Plants and animals mediate early steps of the innate immune response through pathogen recognition receptors (PRRs). PRRs commonly associate with or contain members of a monophyletic group of kinases called the interleukin-1 receptor-associated kinase (IRAK) family that include Drosophila Pelle, human IRAKs, rice XA21 and Arabidopsis FLS2. In mammals, PRRs can also associate with members of the receptor-interacting protein (RIP) kinase family, distant relatives to the IRAK family. Some IRAK and RIP family kinases fall into a small functional class of kinases termed non-RD, many of which do not autophosphorylate the activation loop. We surveyed the yeast, fly, worm, human, Arabidopsis, and rice kinomes (3,723 kinases) and found that despite the small number of non-RD kinases in these genomes (9%–29%), 12 of 15 kinases known or predicted to function in PRR signaling fall into the non-RD class. These data indicate that kinases associated with PRRs can largely be predicted by the lack of a single conserved residue and reveal new potential plant PRR subfamilies.
Animal and plant innate immune systems use a set of similar receptors to recognize disease-causing microbes. These receptors function in pathogen surveillance and are located either at the cell surface or inside the cell. They provide a first line of defense against pathogen attack and rapidly activate defense signaling pathways following infection. Key to their ability to respond to pathogens, a closely related family of proteins called kinases either associate with these receptors or are present as part of the receptors themselves. These kinases face two challenges. The signals must be carefully modulated, as misregulation can result in disease and overall poor health. Second, these signaling systems must be resilient to attempts by pathogens to interfere with and block defense responses. The researchers have found that the kinases that are linked to pathogen receptors and initiate innate immune responses contain an alteration within a critical functional domain of the kinase that is not commonly found in similar kinases that control nondefense pathways. While the exact impact these changes have on kinase function is unclear, these findings provide insight into how these kinases may have evolved to compensate for the unique challenges they face. Moreover, they provide a predictive tool for identifying new candidate kinases that control innate immune responses.
Citation: Dardick C, Ronald P (2006) Plant and Animal Pathogen Recognition Receptors Signal through Non-RD Kinases. PLoS Pathog 2(1): e2. https://doi.org/10.1371/journal.ppat.0020002
Editor: Fred Ausubel, Harvard Medical School, United States of America
Received: July 13, 2005; Accepted: December 14, 2005; Published: January 20, 2006
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: ACF, alternative catalytic function; dsRNA, double-stranded RNA; IRAK, interleukin-1 receptor-associated kinase; LRR, leucine-rich receptor; NBS-LRR, nucleotide binding site leucine-rich receptor; NF-κB, nuclear factor-kappa B; NOD, nucleotide oligomerization domain; PKR, protein kinase R; PRR, pathogen recognition receptor; RIP, receptor-interacting protein; RLCK, receptor-like cytoplasmic kinase; RLP, receptor-like proteins; TLR, Toll-like receptor; TNFR, tumor necrosis factor receptor
Animal and plant innate immune systems use a set of defined pathogen recognition receptors (PRRs), also called pattern recognition receptors, that function as both cell surface and cytoplasmic pathogen surveillance proteins. These receptors provide a first line of defense against pathogen attack and rapidly activate defense signaling pathways following infection (reviewed in ). They play a crucial role in the switch from innate to adaptive immunity in mammals [2–4], and the signaling cascades initiated by PRRs are implicated in a number of human diseases [5–7]. PRR receptors and components of their signaling pathways share remarkable similarities in mammals, plants, and invertebrates. For example, a monophyletic family of serine-threonine kinase domains, the interleukin-1 receptor-associated kinase (IRAK) family (also known as pelle/RLK), including human IRAKs, Drosophila Pelle, and the large family of plant receptor kinases [8–10], either associate with PRRs or are present as intracellular domains of the receptor themselves. These are the first kinases in a kinase signaling cascade that leads, among other known functions, to the initiation of cellular defense responses. A graphic representation of some of the PRRs and PRR-associated kinases that function in innate immune systems in plants, Drosophila, and animals is shown in Figure 1.
Summary of known innate immunity pathways in humans [1,3,11,23,24,26,90], flies [16,], and plants [17,18,19,20]. Kinases are represented by circles. Fly IMD is orthologous to human RIP1 but lacks the kinase domain. Non-RD kinases associate with PRR complexes or, in the case of plants, are intracellular domains of membrane-spanning receptors. Activation of non-RD kinases leads to innate immune signaling via mitogen-activated protein kinase pathways and ultimately stimulates defense-specific transcription factors (blue) in the NF-κB/Rel family or in the case of plant FLS2, the WRKY family.
In animals, recognition of pathogens at the cell surface is largely carried out by members of the Toll-like receptor (TLR) family of PRRs [3,11]. Activation of TLR-1, 2, 4, 5, or 6 triggers a well-characterized signaling pathway that activates nuclear factor-kappa B (NF-κB) transcription factors and leads to a core set of defense responses. In mammals, TLRs associate with IRAK kinases  as well as the IRAK related receptor interacting-protein (RIP) kinases [12,13] through adaptor proteins. While less is known about RIP kinases, IRAK1 becomes activated and rapidly phosphorylated upon pathogen recognition . Activation triggers a downstream signaling pathway that has been well characterized [1,15]. A similar pathway is found in Drosophila, in which the activation of TLR receptors stimulates the recruitment of the IRAK family kinase Pelle .
Plants lack TLRs. Instead, extracellular pathogen recognition is mediated by two known classes of PRRs that lack intracellular kinase domains, serine-threonine receptor kinases and receptor-like proteins (RLPs). Some of the best-studied plant PRRs are the receptor kinases FLS2  and XA21  and the RLPs Cf-9  and XA21D . The signaling pathways of FLS2 and XA21 have been partially characterized [21,22].
Mammals contain at least three classes of intracellular PRRs: TLRs , nucleotide oligomerization domain (NOD) receptors [23–25], and two kinases, protein kinase R (PKR)  and RNAseL , that directly or indirectly detect virus-derived double-stranded RNA (dsRNA). PKR and RNAseL defend against virus attack by shutting down host cell transcriptional machinery and stimulating interferon-mediated innate immune responses that are, in part, controlled by NF-κB . While similar to their cell surface counterparts, TLR-3, 7, 8, and 9 are intracellular receptors that recognize viruses, bacteria, and intracellular parasites . TLR-3, like PKR and RNAseL, responds to viral dsRNA and can activate interferon-mediated pathways . A more recently described class of PRRs is the NOD receptors, which are known to detect bacterial pathogens. RIP2 kinase (also known as RICK and CARDIAC) interacts directly with NOD1  and NOD2  and is required for the activation of NF-κB . This pathway also requires IRAK1; however, the role of IRAK1 in NOD receptor signaling is unknown .
Intracellular recognition of plant pathogens is carried out by NOD receptors (more commonly referred to as nucleotide binding site leucine-rich receptors [NBS-LRRs]) that have been long known to confer strain-specific resistance to numerous viral, bacterial, fungal, and nematode pathogens. Although little is known about NBS-LRR signaling complexes, they are not known to directly associate with and/or signal through kinases. There is a growing body of evidence that many NBS-LRRs indirectly detect pathogens and respond to alterations of host proteins caused by pathogen effectors .
Little is known about how IRAK and RIP family kinases are regulated and stimulated by their cognate receptors. In general, kinase regulation can be achieved through a wide variety of mechanisms and relies on specific phosphorylation events. In response to stimulation, phosphorylation of regulatory domains both within and outside of the kinase domain can alter kinase activity, create substrate-binding sites or disrupt inhibitory protein-protein interactions . In many cases a combination of these mechanisms are employed to tightly regulate kinase activation and signaling. Among these varied strategies, autophosphorylation of a regulatory region termed the activation loop is critical to most kinases . The activation loop, which comprises a short stretch of residues between kinase subdomains VII and VIII, typically resides in close proximity to the kinase active site and has at least two known functions. In some kinases the activation loop blocks substrate access to the active site in the kinase-inactive state and, upon phosphorylation, conformational changes expose the active site . In addition, the activation loop sometimes serves to activate kinases by increasing phosphotransfer efficiency .
Kinases that are regulated by activation loop phosphorylation typically carry a conserved arginine (R) immediately preceding the invariant aspartate in subdomain VI required for catalytic activity . The R is central to cluster of positively charged residues that inhibit catalysis by the adjacent negatively charged aspartate (D) located within the active site and becomes neutralized by contacts with a negatively charged phosphoamino acid(s) in the activation loop. This charge neutralization is essential for proper orientation of the highly conserved D in subdomain VII (DFG motif) that facilitates phosphotransfer . Kinases that are regulated through this mechanism are commonly referred to as RD kinases and are found in bacteria, fungi, plants, and animals.
Conversely, a smaller number of kinases can be grouped into a class referred to as non-RD. Non-RD kinases lack the conserved R in kinase subdomain VI. It has been observed that some non-RD kinases do not autophosphorylate the activation loop and are either constitutively active or regulated through alternative mechanisms . The most notable exceptions fall within the DYRK family of non-RD kinases, which autophosphorylate an activation loop tyrosine residue via an intermediate form that occurs only during translational synthesis . However, in other non-RD kinases the lack of activation loop phosphorylation is consistent with the apparent lack of need for charge neutralization and removal of catalytic inhibition . Despite this commonality, how changes to the RD motif impact kinase function in most cases remains unclear.
The rice PRR XA21 falls into the non-RD class of kinases and is not autophosphorylated in the activation loop in vitro . Likewise, we observed that some related animal kinases, such as IRAK1 and Pelle, were also non-RD. This cross-kingdom correlation prompted us to perform a genome-wide comparison of plant and animal kinases to determine if non-RD motifs are common in kinases associated with pathogen recognition. We surveyed the complement of non-RD kinases among the yeast, fly, worm, human, Arabidopsis, and rice genomes and found that, while less than 20% of all kinases are non-RD, all six plant PRR kinases and six of nine animal PRR-associated cytoplasmic kinases that are known or predicted to transmit PRR signals are non-RD. Furthermore, plant non-RD receptor kinases that function as PRRs show evolutionary expansion patterns characteristic of disease resistance genes.
Non-RD Kinases Are Evolutionarily and Functionally Conserved
We first analyzed the overall distribution, conservation, and functional significance of changes to the RD motif. Kinases were classified based on the presence (RD) or absence (non-RD) of the highly conserved R. In addition, kinases lacking one or more of three highly conserved residues thought to be required for catalytic activity were classified as alternative catalytic function (ACF) (Tables S1, S2, and S3). Together, the yeast, fly, worm, human, Arabidopsis, and rice kinomes are composed of 3,723 kinases. (Detailed information regarding our unpublished rice kinome can be found at http://rkd.ucdavis.edu.) Most kinomes contained relatively few non-RD kinases (9%–16%) with the exception of rice, which had an unusually high number (29%) (Table 1). Of all non-RD kinases, 62% contained a cysteine or glycine, while another 20% contained the hydrophobic amino acids phenylalanine and leucine in substitution of the highly conserved R (Figure 2 and Table S4). These substitutions are predicted to lead to the loss of positive charge and potentially alter kinase regulatory and/or catalytic mechanisms. This limited range of amino acid substitutions suggests that diverse non-RD kinases have adopted similar modifications of the RD motif.
Percentage of Kinase Classes in Eukaryotic Genomes
The frequencies of amino acid residues occurring in each kinome are shown. Single-letter codes for amino acids are listed on the x-axis. The y-axis values represent the number of kinases containing each residue. Non-RD kinases account for 18% of all kinases, with rice containing the vast majority.
In all kinomes, non-RD kinases were distributed among six of the seven kinase groups. The vast majority were found in phylogenetically distinct clusters within the CAMK (calcium/calmodulin-dependent protein kinase), CMGC (containing CDK, MAPK, GSK3, CLK families), CK1 (casein kinase 1), and TKL (tyrosine kinase-like) groups. This is illustrated on the human kinome phylogenetic tree (Figure 3) . Of non-RD kinases, 518 (76%) of 681 were members of conserved kinase families found in all five multicellular eukaryotic genomes surveyed, while 50 (7%) of the 681 were unique to a single kinome. Kinases conserved in at least five kinomes are listed in Table 2, and a complete list of all non-RD kinases can be found in Table S5. Few examples were found of non-RD kinases containing RD counterparts in another organism, suggesting a high degree of evolutionary and functional conservation (Table S5). A small number of non-RD kinases in plants and invertebrates have known functions; however, substantial information is available regarding the functions of human non-RD kinases (Table 3). Not surprisingly, some non-RD kinases, such as MLCK (myosin light chain kinase)  have diverse roles and function in multiple cellular processes. Despite the diversity of functions, 43 of 50 non-RD kinases had known roles in innate immunity, apoptosis, and/or cell cycle control. Markedly infrequent were functions associated with growth, development, cell-to-cell communication, and general stress responses. The finding that non-RD kinases function across a relatively confined set of pathways suggests that these altered kinase regulatory and/or catalytic mechanisms are not widely utilized in cell signaling pathways and may have specifically evolved to control a smaller subset of cellular processes.
A reproduction of the human kinome tree is shown . Kinome dendrogram was reproduced courtesy of Science and Cell Signaling Technology (http://www.cellsignal.com). Names of kinase groups are indicated: AGC (PKA, PKG, and PKC kinases), CMGC (containing CDK, MAPK, GSK3, CLK families), CAMK (calcium/calmodulin-dependent protein kinase), CK1 (casein kinase 1), TK (tyrosine kinases), TKL (tyrosine kinase-like; includes MLKs [mixed lineage kinases], transforming growth factor-β receptor kinases, and Raf kinases), STE (homologs of yeast sterile 7, sterile 11, and sterile 20 kinases). Branches leading to non-RD kinases and ACF kinases are colored red and yellow, respectively. All other branches contain RD kinases. The IRAK and RIP families are indicated above their respective clades. The IRAK family is greatly expanded in Arabidopsis (610) and rice (1,068). Most non-RD kinases are present in phylogenetically linked clusters within the TKL, CAMK, CMGC, and CK1 groups.
Cross-Kingdom Conservation of Non-RD Kinases
Functions of Human Non-RD Kinases
Kinases That Control Early Events of Innate Immunity Signaling in Animals Are Non-RD
To investigate the role of non-RD kinases in animal innate immune systems, we analyzed the known functions of all kinases that lead to the activation of NF-κB in mammals or the orthologous DIF/Relish transcription factors in Drosophila. A complete list of all animal PRR kinases with known functions is shown in Table 4. We found that six of nine kinases known or predicted to associate with PRRs and relay PRR signals were non-RD. Five non-RD kinases in the IRAK and RIP families and one kinase in the “Other” group were found to play prominent roles in early steps of innate immunity pathways (Figure 1, Table 4). These include IRAK1 , Pelle , RIP1 , and RIP2 , which directly associate with NOD and/or TLR type PRRs and play primary roles in signaling (see  and  for reviews on IRAK and RIP kinases). One additional RIP family member, RIP4, has been shown to activate NF-κB when overexpressed . The sixth non-RD kinase, RNAseL, falls into the group “Other” and indirectly responds to viral dsRNA . The three exceptions, IRAK2 (an ACF kinase), IRAK4 (RD) and PKR (RD), have unique or limited roles in PRR signaling. IRAK2 and IRAK4 have a limited ability to propagate PRR signals and/or need non-RD kinases to function. For example, IRAK4 is capable of only weak NF-κB activation in the absence of IRAK1 and is thought to recruit IRAK1 to the PRR complex, where IRAK1 becomes activated and leaves the receptor complex to facilitate downstream signaling [43,44]. IRAK2  is catalytically inactive and mediates NF-κB activation via a MAL/TIRAP (Myd88 adaptor-like protein) that functions in a cell-specific manner to partially control TLR-4 responses . Unlike its human homolog, mouse IRAK2 does not appear to play a role in NF-κB activation , and two splice variants of mouse Irak2 were found to function as negative regulators of innate immune responses . Similarly, PKR, like RNAseL, responds to viral dsRNA; however, PKR kinase activity is not needed to trigger NF-κB activation, suggesting that this function of PKR may be mediated by other proteins such as a non-RD kinase . Of the remaining four IRAK and RIP kinases in humans, three have unknown functions (RIP5 and 6 [non-RD] and RIP7 [RD])  and two act as negative regulators of TLR signaling (IRAK3/IRAKM [ACF] and RIP3 [RD]) [50–52]. Taken together, all NOD- and TLR-type animal PRRs appear to associate with and utilize non-RD IRAK and/or RIP kinases to activate NF-κB pathways, whereas RD and ACF kinases appear to play ancillary roles in signaling.
Other Receptor-Mediated Pathways Leading to NF-κB Activation in Humans Also Utilize Non-RD Kinases
A number of non-PRR receptor-mediated pathways are also known to activate NF-κB in humans, including the tumor necrosis factor receptor (TNFR) family of receptors, which play critical roles in apoptotic signaling as well as in innate and adaptive immune responses (reviewed in ), and the epidermal growth factor receptor . The non-RD kinases IRAK1, RIP1, COT/Tpl-2, and death-associated protein kinase associate with TNFR complexes via TNFR-associated factor, TNFR-associated death domain, and Fas-associated death domain adaptor proteins [55–57]. Similarly, the epidermal growth factor receptor associates with the non-RD kinases RIP1 and NF-κB-inducing kinase; however, unlike TNFRs, it does not appear to require TNFR-associated death domain or Fas-associated death domain adaptor proteins . Most RIP, IRAK, and death-associated protein kinases, with the exception of RIP3–7, share a common domain in the death domain superfamily that includes the death domain, death effector domain, and caspase recruitment domain . These domains mediate protein-protein interactions and link these kinases to receptors and receptor-adaptor proteins that also contain death domains. Therefore, in addition to known PRR-mediated innate immunity pathways, other receptor-mediated pathways leading to NF-κB activation in humans also utilize non-RD kinases.
Non-RD Plant Receptor Kinases Function in Innate Immunity
A survey of IRAK family receptor kinases in plants revealed a perfect correlation between those that function in innate immunity and non-RD motifs (Table 5). Out of 38 receptor kinases with known or implied functions, six are known or presumed to function in disease resistance and act as PRRs. All six fall into the non-RD class. These include the XA21 , XA26 , and Pi-2d [X. Chen, unpublished data] resistance genes from rice, the FLS2  and PR5K  genes from Arabidopsis, and wheat LRK10 , which is linked to a disease resistance locus. The remaining 32 receptor kinases are RD or ACF kinases that function in a wide variety of signaling pathways, including development, pollen recognition, steroid perception, stress/pathogen responses, and interactions with symbiotic organisms. Two RD kinases, ERECTA  and WAKL22 , have been found to incrementally contribute to pathogen resistance in addition to their known roles in development; however, these receptor kinases are not known to function as PRRs, and both ERECTA and WAKL22 were identified as components of quantitative trait loci. Therefore, although diverse IRAK family kinases control many cellular processes in plants, it is clear that as with animal systems, plant PRRs utilize non-RD kinases.
Plant Non-RD Receptor Kinases Are Associated with Innate Immunity
In contrast to animals, plant IRAK family cytoplasmic kinases are not known to associate with and directly relay PRR signals. Of the 22 receptor-like cytoplasmic kinase (RLCK) subfamilies in rice and Arabidopsis (Table S6), only three kinases have been linked to pathogen recognition. PTO and PBS1 are RD kinases that function in concert with the NOD-like NBS-LRR receptors PRF and RPS5, respectively, and provide resistance against bacterial pathogens. Rather than functioning to relay PRR signals, PTO  and PBS1  are thought to be the targets of bacterial effector proteins. A third RLCK, RPG1, contains dual kinase domains (one non-RD and one ACF) and functions in perception of a fungal pathogen . To date, it is not known if RPG1 also requires NBS-LRR receptors to trigger innate immune responses or if RPG1 associates with an RLP. Although it has been repeatedly speculated that RLP-family PRRs that lack kinase domains, such as XA21D  or Cf-9 , transmit signals via receptor kinase or cytoplasmic kinase partners, such partners have not yet been confirmed. Potential candidates include those RLCK family kinases with non-RD domains. For example, the rice RLCK-OS2 subfamily, which is closely related to RPG1, contains single non-RD kinase domains and have unknown functions. RLCKs known to function in non-defense pathways were all found to be RD or ACF kinases (Table S7).
The Correlation between Non-RD Kinases in the IRAK Family and Innate Immunity Is Statistically Significant
IRAK family kinases control diverse cellular processes in humans, Drosophila, and plants and are monophyletic. These characteristics make this group amenable to statistical analysis of kinase function and RD motifs. We analyzed whether the correlation between non-RD kinases in the IRAK family and PRR signaling is statistically significant. Fisher's exact test was used to calculate the probability that the observed correlation can be explained by random associations (Table S7). In contrast to Chi-square analysis, Fisher's exact test accurately predicts probabilities in datasets containing values less than 5. Fifty-two IRAK family kinases were found to have known or implied functions; nine non-RD, seven ACF, and 36 RD. All nine non-RD kinases plus one RD and two ACF kinases were identified as PRRs or are known to associate with PRR complexes. The remaining 40 RD and ACF kinases had a wide variety of cellular and developmental functions. The resulting two-tailed p-value was less than 0.0001, indicating a very high likelihood that the distribution of non-RD IRAK kinases with respect to a role in PRR signaling is not random. Conversely, PRR kinases could not be predicted based on protein domain organization or phylogenetic relationships. A tree showing evolutionary relationships among IRAK kinases with known functions is shown in Table S7. Corroborative trees that include all IRAK kinases are listed in  and .
Expansion of Non-RD IRAK Subfamilies in Rice
The IRAK kinase family in plants consists of numerous receptor and cytoplasmic subfamilies that have been delineated based on phylogenetic analyses and organization of extracellular domains [9,10]. A comparative study of Arabidopsis and rice indicated that IRAK family kinases associated with defense responses have undergone lineage-specific expansions due to both tandem and large scale duplications within the genomes, in some cases resulting in large subfamilies (over 100 kinases) . For example, the LRR XII subfamily that includes the PRRs XA21 and FLS2 contains over 100 members in rice and only eight in Arabidopsis. Similar expansions in plants have also been observed for the NBS-LRR class of PRRs . In contrast, IRAK family kinases associated with development have remained largely unchanged since the last common ancestor of these two highly divergent plant species . We predicted that, if non-RD kinases in plants function as PRRs, they should primarily fall into these expanded subfamilies. In contrast, we predicted that RD subfamilies not associated with innate immunity would tend to show distinct evolutionary patterns, since they are likely under different selection pressures.
Plant IRAK kinase subfamilies were designated as RD, non-RD, or ACF if at least 70% of the members fell into one class (Table S6). Using new data from the assembled Japonica rice genome, we analyzed the composition and chromosomal distribution of all rice and Arabidopsis IRAK kinase subfamilies and selected them based on the following criteria: at least eight members within the subfamily, lineage-specific expansion (i.e., expansion in rice and/or Arabidopsis), and at least one cluster of four or more closely related genes as defined by Holub (Tables S6, S8, and S9) . Chromosomal distributions of all kinases were visualized using Genome Pixelizer . The color-coded images are available in Figure S1 and at our Web site at: http://rkd.ucdavis.edu. The results are summarized in Figure 4.
Rice and Arabidopsis IRAK subfamilies that show evidence of recent expansion are listed on the x-axis. The number of kinases in each subfamily is indicated on the y-axis. Non-RD, mixed, RD, and ACF subfamilies are grouped and separated by dotted lines. Known disease-resistance genes are listed above corresponding subfamilies.
In total, rice contains 456 more IRAK family kinases than Arabidopsis, and expanded non-RD kinase subfamilies accounted for 69% of this difference (313 of the 456). Expanded non-RD subfamilies included all known PRR kinases: XA21 , Xa26 , FLS2 , and Pi-2d [X. Chen, unpublished data], as well as the non-RD RLCK subfamily RLCK-OS2, which is most similar to the resistance gene product RPG1 . Furthermore, all seven non-RD IRAK family receptor kinase subfamilies in rice, and two of three in Arabidopsis, show recent lineage specific expansions. This finding is consistent with the hypothesis that non-RD IRAK subfamilies in plants function in pathogen recognition and innate immunity.
Most IRAK family kinases in animals have known roles in innate immunity. In plants, members of this very large family (in Arabidopsis, 600; in rice, 1,000) play roles in a wide variety of physiological, developmental, and stress pathways in addition to pathogen defense. Here we present evidence that members of the IRAK family controlling innate immune responses can be distinguished from members that control nondefense pathways. We found a significant correlation between the absence of a highly conserved R residue in kinase subdomain VI (non-RD) and a role in the early events of innate immune signaling. These non-RD kinases include human IRAK, Drosophila Pelle, and the plant kinases XA21, XA26, FLS2, RLK10, PR5K, LRK10, RPG1, and PI-D2—all known or predicted to function as PRRs. Additionally, kinases with functions analogous to IRAKs, such as those in the RIP family, also commonly contain non-RD motifs.
Because less than 40 of the hundreds of identified plant receptor kinases have known or predicted functions, we took additional steps to determine the extent of the correlation between non-RD kinases and innate immunity in plants. We found that non-RD PRR kinase subfamilies have evolutionary expansion patterns consistent with the NBS-LRR class of PRRs and show lineage-specific expansions marked by tandem duplications. Recently, a similar analysis demonstrated that the RLP class of PRRs (extracellular receptors that lack kinase domains) show these same expansionary patterns . Known PRR kinase subfamilies were three to 12 times larger in rice than in Arabidopsis. This finding correlates well with previous studies showing that the rice genome contains over three times as many NBS-LRRs . This is also consistent with the fact that only two IRAK family receptors are known or predicted to confer disease resistance in Arabidopsis (FLS2 and PR5K) [17,60], whereas rice and other monocots contain at least five [18,65,59,61, [X. Chen, unpublished data]. All seven of these carry the non-RD motif. Molecular characterization of additional non-RD IRAK receptors will be required to fully comprehend the overall contribution of this class of PRRs to plant innate immunity.
While kinases associated with both plant and animal PRRs carry non-RD motifs, the evolutionary significance of this observation is unclear. Ausubel  recently pointed out the need for caution when discussing the origins of similarities between plant and animal innate immune systems . Speculation that these diverse signaling pathways evolved from a common ancestor has often been overstated as the similarities between plant, fly, and human innate immune systems can largely be explained by convergent evolution. With regard to kinases, it is apparent that in some cases, innate immune pathways have lost and/or added specific kinase domains, making such determinations difficult. For example, the Drosophila counterpart of human RIP kinase, immune deficiency (Imd), lacks the kinase domain. This pathway is a key component of the Drosophila immune system that functions in recognition of gram-negative bacterial pathogens, and thus far no kinases have been identified that associate with the peptidoglycan receptor complex PGRP-LC . Similarly, counterparts of flowering plant NOD-like NBS-LRRs found in the more primitive mosses contain a unique ACF kinase domain that falls within the IRAK family . This kinase-NBS-LRR structure has not been found in flowering plants, suggesting that modern plant NBS-LRRs may have lost the associated kinase. Similarly, the RLP XA21D contains a truncation that results in deletion of the non-RD kinase domain. Despite the loss of the kinase domain, XA21D retains some ability to activate defense responses .
The observation that kinases have been lost from or added to PRR-mediated pathways may also underscore the role of these kinases in signaling. Mutagenesis of the kinase domains of RIP1 , RIP2 , RIP4 , IRAK1 , and XA21  demonstrate that kinase activity is at least partially dispensable for the innate immune response. This a significant departure from conventional roles of kinases in signaling, and, in the cases of IRAK1 and RIP2, evidence suggests they function as phosphorylation-mediated scaffolding proteins as opposed to signaling through phosphorelay cascades, in which receptor signaling leads to kinase activation followed by phosphorylation relay and signal amplification. Rather, auto- and/or transphosphorylation of IRAK1  and RIP2  promote receptor dissociation and subsequent assembly of signaling complexes, the components of which are not typically IRAK1 or RIP1 phosphorylation substrates. Given that these kinases are highly divergent, it seems likely that these potentially similar signaling mechanisms are the result of convergent evolution. In other instances, such as the Drosophila IMD pathway and plant NBS-LRRs and RLPs, assembly of signaling complexes may have evolved to occur in the absence of kinases altogether, hence the lack of these domains .
As with other shared features of plant and animal innate immune systems, our findings are also best explained by convergent evolution. Although IRAK, Pelle, and plant receptor kinases are monophyletic (with respect to other kinase families), they fall into distinct clades. Therefore, IRAK1 and Pelle are not more similar to FLS2 or XA21 than they are to plant IRAK family kinases that control nondefense pathways, such as SYMRK or BRI1 (Table S7). In plants, phylogenetic analysis indicates that the PRR subfamilies LRR-XII (FLS2/XA21), SD-2b (PI-2D), and the putative PRR subfamilies LRK10L-2 (LRK10/PR5K) and RLCK-OS2 (similar to RPG1) may have evolved independently to function in innate immunity. These receptor kinases fall into separate clades, have dissimilar extracellular domains, and contain different amino acid substitutions within the RD motif (Tables S4 and S7) .
Whether through convergence or divergence, it is unclear why modifications of the RD motif have evolved in kinases that activate innate immune pathways. These changes do not likely represent a single mechanistic adaptation and, thus, may produce distinct mechanistic alterations in each kinase. The prevalence of non-RD kinases in PRRs and PRR complexes does, however, imply that RD kinases may not be ideally suited to control some of the early signaling events that lead to activation of NF-κB in animals and defense responses in plants. This is further supported by the finding that non-RD kinases are also common in mammalian receptor-mediated apoptotic responses that also signal through NF-κB. In mammals, precise control of NF-κB pathways is essential, as persistent activation results in chronic inflammatory syndromes and malignancies . NF-κB signaling and its counterparts in plants and invertebrates may have unique strict regulatory requirements that are not satisfied by RD mechanisms. Alternatively, adaptations to the RD motif may have occurred in response to selection pressures imposed by pathogen effector proteins that aim to disrupt defense signaling. Kinases are known targets of a number of bacterial and viral effectors [78,79]. A reduced role for kinase activity in some non-RD kinases, such as IRAK1, RIP1, RIP2, and XA21, may have evolved to avoid pathogen interference. This may also explain the apparent loss of PRR-linked kinases in the Drosophila IMD and plant NBS-LRR pathways, as well as the presence of some catalytically inactive IRAK family members in humans.
One described commonality between diverse non-RD kinases is a lack of activation loop phosphorylation in some, but not all, non-RD kinases . This is also true for a small number of RD kinases, such as the transforming growth factor-β receptor II kinase domain , which maintains a constitutively active configuration through neutralization of the arginine by negatively charged amino acids in the activation loop, and the NFR5 and SYM10 plant IRAK family kinases that lack the activation loop . This function, or lack thereof, has apparently been retained in at least some IRAK family non-RD kinases. In vitro studies have shown that despite the presence of a highly conserved threonine (five amino acids prior to the subdomain VIII motif APE), the activation loop of the rice PRR kinase XA21 is not autophosphorylated . Phosphoproteomics approaches have identified in vivo phosphorylation sites in more than 50 plant receptor kinases . Activation loop phosphorylation was found only in RD and ACF kinases, although non-RD kinases were not well represented in this sample.
Despite indications that the activation loop is not autophosphorylated in some IRAK family non-RD kinases, we found that the highly conserved activation loop threonine is still conserved, indicating that this residue likely plays an important role (unpublished data). Recent data suggest that activation of human IRAK1  and plant IRAK family kinases require this threonine; however, thus far it has only been confirmed as an autophosphorylation site in the plant RD kinases BRI1 , BAK1 , and SYMRK . As it stands now, these data suggest that this residue may play a critical structural role that is independent of its phosphorylation status. Not surprisingly, some IRAK family kinases appear to utilize alternative regulatory mechanisms. A conserved threonine residue located adjacent to kinase subdomain I is also required for catalytic activity of XA21 [W. Song, personal communication], IRAK1 , and SYMRK , but not BRI1 . This residue was shown to be phosphorylated in vitro in IRAK1 and XA21 and was identified as an in vivo site in BRI1; however, mutation to alanine only affected the activities of IRAK, XA21, and SYMRK. With the absence of known structures for any IRAK family kinases, structural studies and further phosphorylation site mapping are needed to illuminate the potential functional significance of changes to the RD motif.
Although non-RD kinases do not typically autophosphorylate the activation loop, in some non-RD kinases this regulatory domain can be transphosphorylated by other kinases. In vitro studies have indicated that the activation loop of IRAK1 could be transphosphorylated by the RD kinase IRAK4 . Likewise, the conserved threonine in the activation loop of the non-RD kinase COT was shown to be constitutively transphosphorylated by an unknown kinase in vivo and was required for both robust kinase activity and activation of NF-κB pathways . The authors point out that this is the only known case in which this highly conserved activation loop residue is transphosphorylated. Therefore, in some non-RD kinases transphosphorylation of the activation loop can alter catalytic activity, but whether this occurs in PRR kinases and how it might relate to signaling remain unclear.
The correlation between non-RD kinases in the IRAK and RIP families and innate immunity provides a predictive tool for the functions of unknown IRAK and RIP kinases (currently over 400), the vast majority of which are plant IRAK family kinases. The finding that a kinase is non-RD is clearly not sufficient information by itself to assess function, nor does it preclude a role for non-RD kinases in nondefense pathways, as is the case with Drosophila Pelle, which also functions in development . However, it can serve as an important indicator of kinase function. For example, during the course of this study, we were able to predict that the RD kinases IRAK4  and RIP3  would have distinct roles (as compared to IRAK1 and RIP1, respectively) in PRR signaling before their putative functions were published. Our analysis also predicts that the Caenorhabditis elegans IRAK family kinase PIK-1 has a likely role in regulating innate immune pathways despite unsuccessful attempts to demonstrate such a role . Similarly, a number of unknown plant IRAK subfamilies can also be predicted to play roles in innate immunity, such as the SD-2a, SD-2b, WAKa, WAKc, RLCK-OS2, and WAKL-OS subfamilies. Indeed, we were informed during the preparation of this manuscript that one of these genes in rice, Pi-2d, encodes a receptor in the SD-2b subfamily and confers resistance to the fungal pathogen Magnaporthe grisea (X. Chen, unpublished data). The ability to draw associations between enzyme signaling pathway functions and specific conserved functional amino acid residues within broad and diverse enzyme families is a powerful bioinformatics tool.
Materials and Methods
Sequence retrieval and annotation.
Amino acid sequences of yeast, fly, worm, and human kinases were obtained from http://www.kinase.com [36,87]. Arabidopsis kinases were downloaded from http://hodgkin.mbu.iisc.ernet.in/~king . Divergent kinases that fall within atypical or histidine kinase families were excluded from all analyses. Kinase classifications were done according to Manning et al. . Names of plant Pelle/RLK subfamilies were derived from Shiu et al.  with some minor modifications. The WAK group was broken down into three phylogenetically distinct subgroups—WAKa, WAKb, and WAKc—to reflect RD and non-RD classes. We also noted that, although the two human kinases SgK496 and SgK288 have both been referred to as RIP5, SgK496 does not appear to fall within the RIP or IRAK subfamilies . The yeast, fly, worm, human, Arabidopsis, and rice kinase domain sequences are available in Datasets S1–S6, respectively.
Characterization of the rice kinome.
Sequences encoding kinases in rice were obtained from The Institute for Genomic Research rice database (http://www.tigr.org/tdb/e2k1/osa1). Kinases were identified using two methods. First, reiterative BLAST searches were conducted using representative Arabidopsis kinase domains from each kinase family. BLAST results for each hit were manually inspected to obtain significant matches. Subsequently, all putative kinase domains were verified using the kinase domain prediction tool available at KinG (http://hodgkin.mbu.iisc.ernet.in/~king) . This rice kinase sequence set was merged with the PlantsP  rice kinome set (M.Gribskov, personal communication) to identify unique kinases. This resulted in 1,508 kinase-encoding genes. Eighty-one genes containing only small kinase fragments were removed for this analysis, and the remaining 1,427 kinases were further analyzed. Kinase family assignments for non-RLKs were obtained from KinG .
Identification of non-RD kinases.
Multiple alignments for each kinome were done using ClustalW. Alignments were manually adjusted to ensure that conserved kinase motifs were accurately aligned. Each kinase was classified based on the presence or absence of the conserved arginine in kinase subdomain VI and the presence or absence of the conserved lysine in kinase subdomain II, aspartic acid in subdomain VI, and aspartic acid in subdomain VII (K/D/D) typically required for catalytic activity. Kinases containing the R were classified as RD, and kinases lacking the R were classified as non-RD. Kinases that lacked one or more of the K/D/D residues were classified as ACF. The three subdomains (II, VI, VII) for each RD, non-RD, and ACF kinase are available in Tables S1, S2, and S3. Subfamilies were classified as being predominantly RD, non-RD, or ACF if more than 70% of the kinases fell into one class (Table S6). This was true for all but five subfamilies (RLCK XV, URKI, DUF26-1h, RLCK-OS1, RLCK IXb), which were classified as “mixed.” A large number of kinases in rice and Arabidopsis were classified as ACF, because these genes encoded protein kinase fragments. While most of these genes in Arabidopsis are authentic, many ACF kinases in rice may have been misclassified because of poor annotation resulting from unavailable EST/cDNA sequences.
Fisher's exact test was performed using SAS version 8.02 procedure FREQ (SAS Institute, Cary, North Carolina, United States). Fisher's exact test was used instead of Chi-square, since Chi-square analysis does not accurately calculate probabilities with values less than 5. All IRAK family kinases with known or predicted functions were placed into two classes: (1) those with known roles in activating innate immunity or (2) those with other functions. Each kinase was then classified as being RD, non-RD, or ACF. The number of kinases falling into each class was determined to produce a contingency table (Table S7) and a two-tailed probability was calculated. This was compared to the same analysis performed by classifying each kinase according to protein domain structure: (1) receptor kinase containing extracellular LRR domains, (2) receptor kinase containing “other” extracellular domains, or (3) cytoplasmic kinase.
Plant IRAK family genomic distributions.
Chromosomal locations of rice kinases were obtained from The Institute for Genomic Research rice database (http://www.tigr.org/tdb/e2k1/osa1). Locations of Arabidopsis kinases were obtained from TAIR (http://www.arabidopsis.org). Chromosomal distributions of rice and Arabidopsis kinases were visualized using Genome Pixelizer . Each kinase is represented by a colored square; kinases are color-coded according to subfamily. This color-coded image map is included in Figure S1, and an interactive version of the rice distribution map is available at http://rkd.ucdavis.edu.
Dataset S1. Amino Acid Sequences of All Kinase Domains within the Yeast Kinome
(38 KB TXT)
Dataset S2. Amino Acid Sequences of All Kinase Domains within the Fly Kinome
(64 KB TXT)
Dataset S3. Amino Acid Sequences of All Kinase Domains within the Worm Kinome
(125 KB TXT)
Dataset S4. Amino Acid Sequences of All Kinase Domains within the Human Kinome
(163 KB EPS)
Dataset S5. Amino Acid Sequences of All Kinase Domains within the Arabidopsis Kinome
(314 KB TXT)
Dataset S6. Amino Acid Sequences of All Kinase Domains within the Rice Kinome
(1.2 MB eps)
Figure S1. Chromosome Map Showing the Chromosome Positions for All Arabidopsis and Rice Kinases
Kinases are color coded according to subfamily. Images were generated using Genome Pixelizer .
(437 KB PPT)
Table S1. RD Kinases in Yeast, Fly, Worm, Human, Arabidopsis, and Rice Kinomes
Motifs for kinase subdomains II, VI, and VII are shown for each kinase.
(1.2 MB XLS)
Table S2. Non-RD Kinases in Yeast, Fly, Worm, Human, Arabidopsis, and Rice Kinomes
Motifs for kinase subdomains II, VI, and VII are shown for each kinase.
(451 KB XLS)
Table S3. ACF Kinases in Yeast, Fly, Worm, Human, Arabidopsis, and Rice Kinomes
Motifs for kinase subdomains II, VI, and VII are shown for each kinase.
(379 KB XLS)
Table S4. Conservation of the R in Kinase Subdomain VI (RD Motif)
The number of kinases in total and in each kinome containing R or other amino acids are listed. RD motif for all kinases is also shown.
(642 KB XLS)
Table S5. Cross-Kingdom Conservation of Non-RD Kinases (Complete Listing)
All non-RD kinases and their counterparts in other kinomes are shown. Kinases are separated into color-coded groups. ACF and RD kinases are indicated when present as homologs of non-RD kinases. Kinomes that lack homologs have been left blank.
(32 KB XLS)
Table S6. Classification of Plant IRAK Subfamilies
Numbers of rice and Arabidopsis RD, non-RD, and ACF kinases are listed for each subfamily. Subfamilies that have recently expanded in rice and/or Arabidopsis are listed separately. Chromosomes containing clusters of four or more closely linked kinases are indicated.
(45 KB XLS)
Table S7. Raw Data Used for Statistical Analysis of IRAK Family Kinase Functions and Non-RD Motifs
The contingency table classes (RD, Non-RD, ACF) or (LRR RK, Other RK, Cytoplasmic) and putative function for each kinase are indicated. The resulting 2 × 2 contingency table is shown. Also, a cladogram depicting phylogenetic relationships between known IRAK family members is shown. The tree was constructed using ClustalW and visualized with Phylodraw v.0.8 (Graphics Application Lab, Pusan National University, Pusan, South Korea). Bootstrap values (100 trials) are written on branch nodes. PRR kinases are indicated with red lines and are found within at least three distinct clades.
(60 KB XLS)
Table S8. Chromosome Numbers and Positions of 5′ End for Each Arabidopsis Kinase
Plant IRAK family kinases are highlighted in yellow.
(1.7 MB XLS)
Table S9. Chromosome Numbers and Positions of 5′ End for Each Rice Kinase
Plant IRAK family kinases are highlighted in yellow.
(884 KB XLS)
We would like to thank J. Chen, University of California Davis, Davis, California, who provided support for data mining and database construction, and designed the RKD Web site. M. Gribskov, Purdue University, West Lafayette, Indiana, graciously merged his rice kinase sequence database with ours and was instrumental in assembling the Japonica rice kinome. O. Shu and R. Buell at The Institute for Genomic Research, Rockville, Maryland, supplied updated gene models and chromosome positions for all rice kinases. R. Bell, Appalachian Fruit Research Station, Kearneysville, West Virginia, assisted with statistical analysis. We would also like to thank M. Fromm, University of Nebraska, Lincoln, Nebraska, for his support with this project, as well as W. Song, University of Florida, Gainesville, Florida, and X. Chen and L. Zhu, Chinese Academy of Sciences, Beijing, for providing unpublished data for XA21 and Pi-d2. Finally, we thank F. Ausubel, Massachusetts General Hospital, Boston, Massachusetts, and T. Richter, University of California Davis, for their guidance in preparing this manuscript. This work was supported by National Institutes of Health grant GM59962 to PR and National Science Foundation grant 0217312 to M. Fromm, University of Nebraska, Lincoln. CD was supported in part by a National Institute of General Medical Sciences, Minority Opportunities in Research Institutional Research and Academic Career Development Award to University of California Davis, grant K12GM00679.
CD and PR conceived, designed, and performed the experiments. CD and PR analyzed the data. CD contributed reagents/materials/analysis tools. CD and PR wrote the paper.
- 1. Akira S, Takeda K (2004) Toll-like receptor signaling. Nat Rev 4: 499–511.S. AkiraK. Takeda2004Toll-like receptor signaling.Nat Rev4499511
- 2. Werling D, Jungi TW (2003) TOLL-like receptors linking innate and adaptive immune response. Vet Immunol Immunopathol 91: 1–12.D. WerlingTW Jungi2003TOLL-like receptors linking innate and adaptive immune response.Vet Immunol Immunopathol91112
- 3. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1: 135–145.R. Medzhitov2001Toll-like receptors and innate immunity.Nat Rev Immunol1135145
- 4. Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: Critical proteins linking innate and acquired immunity. Nat Immunol 2: 675–680.S. AkiraK. TakedaT. Kaisho2001Toll-like receptors: Critical proteins linking innate and acquired immunity.Nat Immunol2675680
- 5. Muir A, Soong G, Sokol S, Reddy B, Gomez MI, et al. (2004) Toll-like receptors in normal and cystic fibrosis airway epithelial cells. Am J Respir Cell Mol Biol 30: 777–83.A. MuirG. SoongS. SokolB. ReddyMI Gomez2004Toll-like receptors in normal and cystic fibrosis airway epithelial cells.Am J Respir Cell Mol Biol3077783
- 6. Laberge MA, Moore KJ, Freeman MW (2005) Atherosclerosis and innate immune signaling. Ann Med 37: 130–140.MA LabergeKJ MooreMW Freeman2005Atherosclerosis and innate immune signaling.Ann Med37130140
- 7. Pande V, Ramos MJ (2005) NF-kappaB in human disease: Current inhibitors and prospects for de novo structure based design of inhibitors. Curr Med Chem 12: 357–374.V. PandeMJ Ramos2005NF-kappaB in human disease: Current inhibitors and prospects for de novo structure based design of inhibitors.Curr Med Chem12357374
- 8. Mushegian A, Medzhitov R (2001) Evolutionary perspective on innate immune recognition. J Cell Biol 155: 705–710.A. MushegianR. Medzhitov2001Evolutionary perspective on innate immune recognition.J Cell Biol155705710
- 9. Shiu S, Bleecker AB (2001) Receptor-like kinases from Arabidopsis form a monophyletic gene family related to animal receptor kinases. Proc Natl Acad Sci U S A 98: 10763–10768.S. ShiuAB Bleecker2001Receptor-like kinases from Arabidopsis form a monophyletic gene family related to animal receptor kinases.Proc Natl Acad Sci U S A981076310768
- 10. Shiu SH, Karlowski WM, Pan R, Tzeng YH, Mayer KF, et al. (2004) Comparative analysis of the receptor-like kinase family in Arabidopsis and rice. Plant Cell 16: 1220–1234.SH ShiuWM KarlowskiR. PanYH TzengKF Mayer2004Comparative analysis of the receptor-like kinase family in Arabidopsis and rice.Plant Cell1612201234
- 11. Hopkins PA, Sriskandan S (2005) . Hopkins PA, Sriskandan S (2005) Mammalian Toll-like receptors: To immunity and beyond. 140. : 395–340.PA HopkinsS. Sriskandan2005.Hopkins PA, Sriskandan S (2005) Mammalian Toll-like receptors: To immunity and beyond140395340
- 12. Kobayashi K, Inohara N, Hernandez LD, Galán JE, Núñez G, et al. (2002) RICK/Rip2/CARDIAK mediates signaling for receptors of the innate and adaptive immune systems. Nature 416: 194–198.K. KobayashiN. InoharaLD HernandezJE GalánG. Núñez2002RICK/Rip2/CARDIAK mediates signaling for receptors of the innate and adaptive immune systems.Nature416194198
- 13. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, et al. (2004) RIP1 is an essential mediator of Toll-like receptor 3-induced NF-κB activation. Nat Immunol 5: 503–507.E. MeylanK. BurnsK. HofmannV. BlancheteauF. Martinon2004RIP1 is an essential mediator of Toll-like receptor 3-induced NF-κB activation.Nat Immunol5503507
- 14. Kollewe C, Mackensen A, Neumann D, Knop J, Cao P, et al. (2004) Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. J Biol Chem 279: 5227–5236.C. KolleweA. MackensenD. NeumannJ. KnopP. Cao2004Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling.J Biol Chem27952275236
- 15. Jiang Z, Ninomiya-Tsuji J, Qian Y, Matsumoto K, Li X (2002) Interleukin-1 (Il-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol. Mol Cell Biol 22: 7158–7167.Z. JiangJ. Ninomiya-TsujiY. QianK. MatsumotoX. Li2002Interleukin-1 (Il-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol.Mol Cell Biol2271587167
- 16. Tanji T, Ip YT (2005) Regulators of the Toll and Imd pathways in the Drosophila innate immune response. Trends Immunol 26: 193–198.T. TanjiYT Ip2005Regulators of the Toll and Imd pathways in the Drosophila innate immune response.Trends Immunol26193198
- 17. Gomez-Gomez L, Boller T (2002) Flagellin perception: A paradigm for innate immunity. Trends Plant Sci 7: 251–256.L. Gomez-GomezT. Boller2002Flagellin perception: A paradigm for innate immunity.Trends Plant Sci7251256
- 18. Song WY, Wang GL, Chen LL, Kim HS, Pi LY, et al. (1995) A receptor kinase-like protein encoded by the rice disease resistance gene, Xa21. Science 270: 1804–1806.WY SongGL WangLL ChenHS KimLY Pi1995A receptor kinase-like protein encoded by the rice disease resistance gene, Xa21.Science27018041806
- 19. Jones DA, Thomas CM, Hammond-Kosack KE, Balint-Kurti PJ, Jones JD (1994) Isolation of the tomato Cf-9 gene for resistance to Cladosporium fulvum by transposon tagging. Science 266: 789–793.DA JonesCM ThomasKE Hammond-KosackPJ Balint-KurtiJD Jones1994Isolation of the tomato Cf-9 gene for resistance to Cladosporium fulvum by transposon tagging.Science266789793
- 20. Wang GL, Ruan DL, Song WY, Sideris S, Chen L, et al. (1998) Xa21D encodes a receptor-like molecule with a leucine-rich repeat domain that determines race-specific recognition and is subject to adaptive evolution. Plant Cell 10: 765–779.GL WangDL RuanWY SongS. SiderisL. Chen1998Xa21D encodes a receptor-like molecule with a leucine-rich repeat domain that determines race-specific recognition and is subject to adaptive evolution.Plant Cell10765779
- 21. Asai T, Tena G, Plotnikova J, Willmann MR, Chiu W, et al. (2002) MAP kinase signaling cascade in Arabidopsis innate immunity. Nature 415: 977–983.T. AsaiG. TenaJ. PlotnikovaMR WillmannW. Chiu2002MAP kinase signaling cascade in Arabidopsis innate immunity.Nature415977983
- 22. Chern M, Canlas PE, Fitzgerald HA, Ronald PC (2005) Rice NRR, a negative regulator of disease resistance, interacts with Arabidopsis NPR1 and rice NH1. Plant J 43: 623–635.M. ChernPE CanlasHA FitzgeraldPC Ronald2005Rice NRR, a negative regulator of disease resistance, interacts with Arabidopsis NPR1 and rice NH1.Plant J43623635
- 23. Bertin J, Nir WJ, Fischer CM, Tayber OV, Errada PR, et al. (1999) Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-κB. J Biol Chem 274: 12955–12958.J. BertinWJ NirCM FischerOV TayberPR Errada1999Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-κB.J Biol Chem2741295512958
- 24. Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, et al. (2001) Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-κB. J Biol Chem 276: 4812–4818.Y. OguraN. InoharaA. BenitoFF ChenS. Yamaoka2001Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-κB.J Biol Chem27648124818
- 25. Opitz B, Puschel A, Schmeck B, Hock A, Rosseau S, et al. (2004) Nucleotide-binding oligomerization domain proteins are innate immune receptors for internalized Streptococcus pneumoniae. J Biol Chem 279: 36426–36432.B. OpitzA. PuschelB. SchmeckA. HockS. Rosseau2004Nucleotide-binding oligomerization domain proteins are innate immune receptors for internalized Streptococcus pneumoniae.J Biol Chem2793642636432
- 26. Meurs E, Chong K, Galabru J, Thomas NS, Kerr IM, et al. (1990) Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell 62: 379–390.E. MeursK. ChongJ. GalabruNS ThomasIM Kerr1990Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon.Cell62379390
- 27. Hovanessian AG (1991) Interferon-induced and double-stranded RNA activated enzymes: A specific protein kinase and 29,59-oligoadenylate synthetases. J Interferon Res 11: 199–205.AG Hovanessian1991Interferon-induced and double-stranded RNA activated enzymes: A specific protein kinase and 29,59-oligoadenylate synthetases.J Interferon Res11199205
- 28. Iordonov MS, Wong J, Bell JC, Magun BE (2001) Activation of NF-κB by double-stranded RNA (dsRNA) in the absence of protein kinase R and RNase L demonstrates the existence of two separate dsRNA-triggered antiviral programs. Mol Cell Biol 21: 61–72.MS IordonovJ. WongJC BellBE Magun2001Activation of NF-κB by double-stranded RNA (dsRNA) in the absence of protein kinase R and RNase L demonstrates the existence of two separate dsRNA-triggered antiviral programs.Mol Cell Biol216172
- 29. Moynagh PN (2005) TLR signalling and activation of IRFs: Revisiting old friends from the NF-κB pathway. Trends Immunol 26: 469–476.PN Moynagh2005TLR signalling and activation of IRFs: Revisiting old friends from the NF-κB pathway.Trends Immunol26469476
- 30. Shao F, Golstein C, Ade J, Stoutemyer M, Dixon JE, et al. (2003) Cleavage of Arabidopsis PBS1 by a bacterial type III effector. Science 301: 1230–1233.F. ShaoC. GolsteinJ. AdeM. StoutemyerJE Dixon2003Cleavage of Arabidopsis PBS1 by a bacterial type III effector.Science30112301233
- 31. Johnson LN, Nobel MEM, Owen DJ (1996) Active and Inactive Protein Kinases: Structural Basis for Regulation. Cell 85: 149–158.LN JohnsonMEM NobelDJ Owen1996Active and Inactive Protein Kinases: Structural Basis for Regulation.Cell85149158
- 32. Adams JA (2003) Activation loop phosphorylation and catalysis in protein kinases: Is there functional evidence for the autoinhibitor model? Biochemistry 42: 601–607.JA Adams2003Activation loop phosphorylation and catalysis in protein kinases: Is there functional evidence for the autoinhibitor model?Biochemistry42601607
- 33. Krupa A, Preethi G, Srinivasan N (2004) Structural modes of stabilization of permissive phosphorylation sites in protein kinases: Distinct strategies in Ser/Thr and Tyr kinases. J Mol Biol 339: 1025–1039.A. KrupaG. PreethiN. Srinivasan2004Structural modes of stabilization of permissive phosphorylation sites in protein kinases: Distinct strategies in Ser/Thr and Tyr kinases.J Mol Biol33910251039
- 34. Lochhead PA, Sibbet G, Morrice N, Cleghon V (2005) Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell 121: 925–936.PA LochheadG. SibbetN. MorriceV. Cleghon2005Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs.Cell121925936
- 35. Liu G, Pi L, Walker J, Ronald P (2002) Biochemical characterization of the kinase domain of the rice disease resistance receptor-like kinase XA21. J Biol Chem 277: 20264–20269.G. LiuL. PiJ. WalkerP. Ronald2002Biochemical characterization of the kinase domain of the rice disease resistance receptor-like kinase XA21.J Biol Chem2772026420269
- 36. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298: 1912–1934.G. ManningDB WhyteR. MartinezT. HunterS. Sudarsanam2002The protein kinase complement of the human genome.Science29819121934
- 37. Jin Y, Atkinson SJ, Marrs JA, Gallagher PJ (2001) Myosin II light chain phosphorylation regulates membrane localization and apoptotic signaling of tumor necrosis factor receptor-1. J Biol Chem 276: 30342–30349.Y. JinSJ AtkinsonJA MarrsPJ Gallagher2001Myosin II light chain phosphorylation regulates membrane localization and apoptotic signaling of tumor necrosis factor receptor-1.J Biol Chem2763034230349
- 38. Cao Z, Henzel WJ, Gao X (1996) IRAK: A kinase associated with the interleukin-1 receptor. Science 271: 1128–1231.Z. CaoWJ HenzelX. Gao1996IRAK: A kinase associated with the interleukin-1 receptor.Science27111281231
- 39. Shen B, Manley JL (1998) Phosphorylation modulates direct interactions between the Toll receptor, Pelle kinase and Tube. Development 125: 4719–4728.B. ShenJL Manley1998Phosphorylation modulates direct interactions between the Toll receptor, Pelle kinase and Tube.Development12547194728
- 40. Janssens S, Beyaert R (2003) Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell 11: 293–302.S. JanssensR. Beyaert2003Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members.Mol Cell11293302
- 41. Meylan E, Tschopp J (2005) The RIP kinases: Crucial integrators of cellular stress. Trends Biochem Sci 30: 151–159.E. MeylanJ. Tschopp2005The RIP kinases: Crucial integrators of cellular stress.Trends Biochem Sci30151159
- 42. Meylan E, Martinon F, Thome M, Gschwendt M, Tschopp J (2002) RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF-kappaB and is processed during apoptosis. EMBO Rep 3: 1201–1208.E. MeylanF. MartinonM. ThomeM. GschwendtJ. Tschopp2002RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF-kappaB and is processed during apoptosis.EMBO Rep312011208
- 43. Li S, Strelow A, Fontana EJ, Wesche H (2002) IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase. Proc Natl Acad Sci U S A 99: 5567–5572.S. LiA. StrelowEJ FontanaH. Wesche2002IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase.Proc Natl Acad Sci U S A9955675572
- 44. Qin J, Jian Z, Qian Y, Casanova J, Li X (2004) IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness. J Biol Chem 279: 26748–26753.J. QinZ. JianY. QianJ. CasanovaX. Li2004IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness.J Biol Chem2792674826753
- 45. Muzio M, Ni J, Feng P, Dixit VM (1997) IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278: 1612–1615.M. MuzioJ. NiP. FengVM Dixit1997IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling.Science27816121615
- 46. Andreakos E, Sacre SM, Smith C, Lundberg A, Kiriakidis S, et al. (2004) Distinct pathways of LPS-induced NF-kappa B activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP. Blood 103: 2229–2237.E. AndreakosSM SacreC. SmithA. LundbergS. Kiriakidis2004Distinct pathways of LPS-induced NF-kappa B activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP.Blood10322292237
- 47. Rosati O, Martin MU (2002) Identification and characterization of murine IRAK-2. Biochem Biophys Res Commun 297: 52–58.O. RosatiMU Martin2002Identification and characterization of murine IRAK-2.Biochem Biophys Res Commun2975258
- 48. 48 Hardy MP, O'Neill LA (2004) The murine IRAK2 gene encodes four alternatively spliced isoforms, two of which are inhibitory. J Biol Chem 279: 27699–27708.
- 49. Donzé O, Deng J, Curran J, Sladek R, Picard D, et al. (2004) The protein kinase PKR: A molecular clock that sequentially activates survival and death programs. EMBO J 23: 564–571.O. DonzéJ. DengJ. CurranR. SladekD. Picard2004The protein kinase PKR: A molecular clock that sequentially activates survival and death programs.EMBO J23564571
- 50. Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, et al. (1999) IRAK-M is a novel member of the pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 274: 19403–19410.H. WescheX. GaoX. LiCJ KirschningGR Stark1999IRAK-M is a novel member of the pelle/interleukin-1 receptor-associated kinase (IRAK) family.J Biol Chem2741940319410
- 51. Kobayashi K, Hernandez LD, Galán JE, Janeway CA, Medzhitov R, et al. (2002) IRAK-M is a negative regulator of Toll-like teceptor signaling. Cell 110: 191–202.K. KobayashiLD HernandezJE GalánCA JanewayR. Medzhitov2002IRAK-M is a negative regulator of Toll-like teceptor signaling.Cell110191202
- 52. Sun X, Yin J, Starovasnik MA, Fairbrother WJ, Dixit VM (2002) Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3. J Biol Chem 277: 9505–9511.X. SunJ. YinMA StarovasnikWJ FairbrotherVM Dixit2002Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3.J Biol Chem27795059511
- 53. Kobayashi T, Walsh MC, Choi Y (2004) The role of TRAF6 in signal transduction and the immune response. Microbes Infect 6: 1333–1338.T. KobayashiMC WalshY. Choi2004The role of TRAF6 in signal transduction and the immune response.Microbes Infect613331338
- 54. Habib AA, Chatterjee S, Park SK, Ratan RR, Lefebvre S, et al. (2001) The epidermal growth factor receptor engages receptor interacting protein nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B. J Biol Chem 276: 8865–8874.AA HabibS. ChatterjeeSK ParkRR RatanS. Lefebvre2001The epidermal growth factor receptor engages receptor interacting protein nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B.J Biol Chem27688658874
- 55. Liu Z (2005) Molecular mechanism of TNF signaling and beyond. Cell Research 15: 24–27.Z. Liu2005Molecular mechanism of TNF signaling and beyond.Cell Research152427
- 56. Chan H, Reed JC (2005) TRAF-dependent association of protein kinase Tpl2/COT1 (MAP3K8) with CD40. Biochem Biophys Res Commun 328: 198–205.H. ChanJC Reed2005TRAF-dependent association of protein kinase Tpl2/COT1 (MAP3K8) with CD40.Biochem Biophys Res Commun328198205
- 57. Cohen O, Inbal B, Kissil JL, Raveh T, Berissi H, et al. (1999) DAP-kinase participates in TNF-α- and Fas-induced apoptosis and its function requires the death domain. J Cell Biol 146: 141–148.O. CohenB. InbalJL KissilT. RavehH. Berissi1999DAP-kinase participates in TNF-α- and Fas-induced apoptosis and its function requires the death domain.J Cell Biol146141148
- 58. Weber CH, Vincenz C (2001) The death domain superfamily: A tale of two interfaces? Trends Biochem Sci 26: 475–481.CH WeberC. Vincenz2001The death domain superfamily: A tale of two interfaces?Trends Biochem Sci26475481
- 59. Sun X, Cao Y, Yang Z, Xu C, Li X, et al. (2004) Xa26, a gene conferring resistance to Xanthomonas oryzae pv. oryzae in rice, encodes an LRR receptor kinase-like protein. Plant Journal 37: 517–527.X. SunY. CaoZ. YangC. XuX. Li2004Xa26, a gene conferring resistance to Xanthomonas oryzae pv. oryzae in rice, encodes an LRR receptor kinase-like protein.Plant Journal37517527
- 60. Wang X, Zafian P, Choudhary M, Lawton M (1996) The PR5K receptor protein kinase from Arabidopsis thaliana is structurally related to a family of plant defense proteins. Proc Natl Acad Sci U S A 93: 2598–2602.X. WangP. ZafianM. ChoudharyM. Lawton1996The PR5K receptor protein kinase from Arabidopsis thaliana is structurally related to a family of plant defense proteins.Proc Natl Acad Sci U S A9325982602
- 61. Feuillet C, Schachermayr G, Keller B (1997) Molecular cloning of a new receptor-like kinase gene encoded at the Lr10 disease resistance locus of wheat. Plant J 11: 45–52.C. FeuilletG. SchachermayrB. Keller1997Molecular cloning of a new receptor-like kinase gene encoded at the Lr10 disease resistance locus of wheat.Plant J114552
- 62. Godiard L, Sauviac L, Torii KU, Grenon O, Mangin B, et al. (2003) ERECTA, an LRR receptor-like kinase protein controlling development pleiotropically affects resistance to bacterial wilt. Plant J 36: 353–365.L. GodiardL. SauviacKU ToriiO. GrenonB. Mangin2003ERECTA, an LRR receptor-like kinase protein controlling development pleiotropically affects resistance to bacterial wilt.Plant J36353365
- 63. Diener AC, Ausubel FM (2005) RESISTANCE TO FUSARIUM OXYSPORUM 1, a dominant Arabidopsis disease-resistance gene, is not race specific. Genetics 171: 305–321.AC DienerFM Ausubel2005RESISTANCE TO FUSARIUM OXYSPORUM 1, a dominant Arabidopsis disease-resistance gene, is not race specific.Genetics171305321
- 64. Wu A, Andriotis VME, Durrant MC, Rathjen JP (2004) A patch of surface-exposed residues mediates negative regulation of immune signaling by tomato Pto kinase. Plant Cell 16: 2809–2821.A. WuVME AndriotisMC DurrantJP Rathjen2004A patch of surface-exposed residues mediates negative regulation of immune signaling by tomato Pto kinase.Plant Cell1628092821
- 65. Brueggeman R, Rostoks N, Kudrna D, Kilian A, Han F, et al. (2002) The barley stem rust-resistance gene Rpg1 is a novel disease-resistance gene with homology to receptor kinases. Proc Natl Acad Sci U S A 99: 9328–9333.R. BrueggemanN. RostoksD. KudrnaA. KilianF. Han2002The barley stem rust-resistance gene Rpg1 is a novel disease-resistance gene with homology to receptor kinases.Proc Natl Acad Sci U S A9993289333
- 66. Zhou T, Wang Y, Chen JQ, Araki H, Jing Z, et al. (2004) Genome-wide identification of NBS genes in japonica rice reveals significant expansion of divergent non-TIR NBS-LRR genes. Mol Genet Genomics 271: 402–415.T. ZhouY. WangJQ ChenH. ArakiZ. Jing2004Genome-wide identification of NBS genes in japonica rice reveals significant expansion of divergent non-TIR NBS-LRR genes.Mol Genet Genomics271402415
- 67. Holub EB (2001) The arms race is ancient history in Arabidopsis, the wildflower. Nature 2: 516–527.EB Holub2001The arms race is ancient history in Arabidopsis, the wildflower.Nature2516527
- 68. Kozik A, Kochetkova E, Michelmore RW (2002) GenomePixelizer—A visualization program for comparative genomics within and between species. Bioinformatics 18: 335–336.A. KozikE. KochetkovaRW Michelmore2002GenomePixelizer—A visualization program for comparative genomics within and between species.Bioinformatics18335336
- 69. Fritz-Laylin LK, Krishnamurthy N, Tör M, Sjölander KV, Jones JDG (2005) Phylogenomic analysis of the receptor-like proteins of rice and Arabidopsis. Plant Physiol 138: 611–623.LK Fritz-LaylinN. KrishnamurthyM. TörKV SjölanderJDG Jones2005Phylogenomic analysis of the receptor-like proteins of rice and Arabidopsis.Plant Physiol138611623
- 70. Ausubel FM (2005) Are innate immune signaling pathways in plants and animals conserved? Nat Immunol 6: 973–979.FM Ausubel2005Are innate immune signaling pathways in plants and animals conserved?Nat Immunol6973979
- 71. Akita M, Valkonen JP (2002) A novel gene family in moss (Physcomitrella patens) shows sequence homology and a phylogenetic relationship with the TIR-NBS class of plant disease resistance genes. J Mol Evol 55: 595–605.M. AkitaJP Valkonen2002A novel gene family in moss (Physcomitrella patens) shows sequence homology and a phylogenetic relationship with the TIR-NBS class of plant disease resistance genes.J Mol Evol55595605
- 72. Ting AT, Pimentel-Muinos FX, Seed B (1996) RIP mediates tumor necrosis factor receptor 1 activation of NF-κB but not Fas/APO-1-initiated apoptosis. EMBO J 15: 6189–6196.AT TingFX Pimentel-MuinosB. Seed1996RIP mediates tumor necrosis factor receptor 1 activation of NF-κB but not Fas/APO-1-initiated apoptosis.EMBO J1561896196
- 73. Lu C, Wang A, Dorsch M, Tian J, Nagashima K, et al. (2005) Participation of Rip2 in lipopolysaccharide signaling is independent of its kinase activity. J Biol Chem 280: 16278–16283.C. LuA. WangM. DorschJ. TianK. Nagashima2005Participation of Rip2 in lipopolysaccharide signaling is independent of its kinase activity.J Biol Chem2801627816283
- 74. Moran ST, Haider K, Ow Y, Milton P, Chen L, et al. (2003) Protein kinase C-associated kinase can activate NFkappaB in both a kinase-dependent and a kinase-independent manner. J Biol Chem 278: 21526–21533.ST MoranK. HaiderY. OwP. MiltonL. Chen2003Protein kinase C-associated kinase can activate NFkappaB in both a kinase-dependent and a kinase-independent manner.J Biol Chem2782152621533
- 75. Knop J, Martin MU (1999) Effects of IL-1 receptor-associated kinase (IRAK) expression on IL-1 signaling are independent of its kinase activity. FEBS Lett 448: 81–85.J. KnopMU Martin1999Effects of IL-1 receptor-associated kinase (IRAK) expression on IL-1 signaling are independent of its kinase activity.FEBS Lett4488185
- 76. Andaya CB, Ronald PC (2003) A catalytically impaired mutant of rice Xa21 receptor kinase confers partial resistance to Xanthomonas oryzae pv. oryzae. Physiol Mol Plant Pathol 62: 203–208.CB AndayaPC Ronald2003A catalytically impaired mutant of rice Xa21 receptor kinase confers partial resistance to Xanthomonas oryzae pv. oryzae.Physiol Mol Plant Pathol62203208
- 77. Chen F, Castranova V, Shi X, Demers LM (1999) New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem 45: 7–17.F. ChenV. CastranovaX. ShiLM Demers1999New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases.Clin Chem45717
- 78. Espinosa A, Alfano JR (2004) Disabling surveillance: Bacterial type III secretion system effectors that suppress innate immunity. Cell Microbiol 6: 1011–1027.A. EspinosaJR Alfano2004Disabling surveillance: Bacterial type III secretion system effectors that suppress innate immunity.Cell Microbiol610111027
- 79. Goodbourn S, Didcock L, Randall RE (2000) Interferons: Cell signalling, immune modulation, antiviral response and virus countermeasures. J Gen Virol 81: 2341–2364.S. GoodbournL. DidcockRE Randall2000Interferons: Cell signalling, immune modulation, antiviral response and virus countermeasures.J Gen Virol8123412364
- 80. Stamos J, Sliwkowski MX, Eigenbrot C (2002) Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol Chem 277: 46265–46272.J. StamosMX SliwkowskiC. Eigenbrot2002Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.J Biol Chem2774626546272
- 81. Madsen EB, Madsen LH, Radutoiu S, Olbryt M, Rakwalska M, et al. (2003) A receptor kinase gene of the LysM type is involved in legume perception of rhizobial signals. Nature 425: 637–640.EB MadsenLH MadsenS. RadutoiuM. OlbrytM. Rakwalska2003A receptor kinase gene of the LysM type is involved in legume perception of rhizobial signals.Nature425637640
- 82. Nühse TS, Stensballe A, Jensen ON, Peck SC (2004) Phosphoproteomics of the Arabidopsis plasma membrane and a new phosphorylation site database. Plant Cell 16: 2394–2405.TS NühseA. StensballeON JensenSC Peck2004Phosphoproteomics of the Arabidopsis plasma membrane and a new phosphorylation site database.Plant Cell1623942405
- 83. Wang X, Goshe MB, Soderblom EJ, Phinney BS, Kuchar JA, et al. (2005) Identification and functional analysis of in vivo phosphorylation sites of the Arabidopsis BRASSINOSTEROID-INSENSITIVE1 receptor kinase. Plant Cell 17: 1685–1703.X. WangMB GosheEJ SoderblomBS PhinneyJA Kuchar2005Identification and functional analysis of in vivo phosphorylation sites of the Arabidopsis BRASSINOSTEROID-INSENSITIVE1 receptor kinase.Plant Cell1716851703
- 84. Yoshida S, Parniske M (2005) Regulation of plant symbiosis receptor kinase through serine and threonine phosphorylation. J Biol Chem 280: 9203–9209.S. YoshidaM. Parniske2005Regulation of plant symbiosis receptor kinase through serine and threonine phosphorylation.J Biol Chem28092039209
- 85. Luciano BS, Hsu S, Channavajhala PL, Lin L, Cuozzo JW (2004) Phosphorylation of threonine 290 in the activation loop of Tp12/Cot is necessary but not sufficient for kinase activity. J Biol Chem 279: 52117–52123.BS LucianoS. HsuPL ChannavajhalaL. LinJW Cuozzo2004Phosphorylation of threonine 290 in the activation loop of Tp12/Cot is necessary but not sufficient for kinase activity.J Biol Chem2795211752123
- 86. Pujol N, Link EM, Liu LX, Kurz CL, Alloing G, et al. (2001) A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans. Curr Biol 11: 809–821.N. PujolEM LinkLX LiuCL KurzG. Alloing2001A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans.Curr Biol11809821
- 87. Manning G, Plowman GD, Hunter T, Sudarsanam S (2002) Evolution of protein kinase signaling from yeast to man. Trends Biochem Sci 27: 514–520.G. ManningGD PlowmanT. HunterS. Sudarsanam2002Evolution of protein kinase signaling from yeast to man.Trends Biochem Sci27514520
- 88. Krupa A, Abhinandan KR, Srinivasan N (2004) KinG: A database of protein kinases in genomes. Nucleic Acids Res 32: 153–155.A. KrupaKR AbhinandanN. Srinivasan2004KinG: A database of protein kinases in genomes.Nucleic Acids Res32153155
- 89. Tchieu JH, Fana F, Fink JL, Harper J, Nair TM, et al. (2003) The PlantsP and PlantsT functional genomics databases. Nucleic Acids Res 31: 342–344.JH TchieuF. FanaJL FinkJ. HarperTM Nair2003The PlantsP and PlantsT functional genomics databases.Nucleic Acids Res31342344
- 90. Liew FY, Xu D, Brint EK, O'Neill LA (2005) Negative regulation of Toll like receptor mediated immune responses. Nat Rev Immunol 5: 446–458.FY LiewD. XuEK BrintLA O'Neill2005Negative regulation of Toll like receptor mediated immune responses.Nat Rev Immunol5446458
- 91. Becker W, Joost HG (1999) Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity. Prog Nucleic Acid Res Mol Biol 62: 1–17.W. BeckerHG Joost1999Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity.Prog Nucleic Acid Res Mol Biol62117
- 92. Gross T, Lutzelberger M, Weigmann H, Klingenhoff A, Shenoy S, et al. (1997) Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue. Nucleic Acids Res 25: 1028–1035.T. GrossM. LutzelbergerH. WeigmannA. KlingenhoffS. Shenoy1997Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue.Nucleic Acids Res2510281035
- 93. Prasad J, Manley JL (2003) Regulation and substrate specificity of the SR protein kinase Clk/Sty. Mol Cell Biol 23: 4139–4149.J. PrasadJL Manley2003Regulation and substrate specificity of the SR protein kinase Clk/Sty.Mol Cell Biol2341394149
- 94. Siebel CW, Feng L, Guthrie C, Fu XD (1999) Conservation in budding yeast of a kinase specific for SR splicing factors. Proc Natl Acad Sci U S A 96: 5440–5445.CW SiebelL. FengC. GuthrieXD Fu1999Conservation in budding yeast of a kinase specific for SR splicing factors.Proc Natl Acad Sci U S A9654405445
- 95. Fisk HA, Mattison CP, Winey M (2004) A field guide to the Mps1 family of protein kinases. Cell Cycle 3: 439–442.HA FiskCP MattisonM. Winey2004A field guide to the Mps1 family of protein kinases.Cell Cycle3439442
- 96. Chan GK, Yen TJ (2003) The mitotic checkpoint: A signaling pathway that allows a single unattached kinetochore to inhibit mitotic exit. Prog Cell Cycle Res 5: 431–439.GK ChanTJ Yen2003The mitotic checkpoint: A signaling pathway that allows a single unattached kinetochore to inhibit mitotic exit.Prog Cell Cycle Res5431439
- 97. Booher RN, Deshaies RJ, Kirschner MW (1993) Properties of Saccharomyces cervisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins. EMBO J 12: 3417–3426.RN BooherRJ DeshaiesMW Kirschner1993Properties of Saccharomyces cervisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins.EMBO J1234173426
- 98. Herman PK, Stck JH, Emr SD (1991) A genetic and structural analysis of the yeast Vps15 protein kinase: evidence for a direct role of Vps15p in vacuolar protein delivery. EMBO J 10: 4049–4060.PK HermanJH StckSD Emr1991A genetic and structural analysis of the yeast Vps15 protein kinase: evidence for a direct role of Vps15p in vacuolar protein delivery.EMBO J1040494060
- 99. Facchin S, Lopreiato R, Ruzzene M, Marin O, Sartori G, et al. (2003) Functional homology between yeast piD261/Bud32 and human PRPK: Both phosphorylate p53 and PRPK partially complements piD261/Bud32 deficiency. FEBS Lett 549: 63–66.S. FacchinR. LopreiatoM. RuzzeneO. MarinG. Sartori2003Functional homology between yeast piD261/Bud32 and human PRPK: Both phosphorylate p53 and PRPK partially complements piD261/Bud32 deficiency.FEBS Lett5496366
- 100. Han Z, Saam JR, Adams HP, Mango SE, Schumacher JM (2003) The C. elegans Tousled-like Kinase (TLK-1) has an essential role in transcription. Curr Biol 13: 1921–1929.Z. HanJR SaamHP AdamsSE MangoJM Schumacher2003The C. elegans Tousled-like Kinase (TLK-1) has an essential role in transcription.Curr Biol1319211929
- 101. Gaozza E, Baker SJ, Vora RK, Reddy EP (1997) AATYK: A novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells. Oncogene 15: 3127–3135.E. GaozzaSJ BakerRK VoraEP Reddy1997AATYK: A novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells.Oncogene1531273135
- 102. Gorgoulis VG, Zacharatos P, Mariatos G, Liloglou T, Kokotas S, et al. (2001) Deregulated Epression of c-mos in non-small cell lung carcinomas: Relationship with p53 status, genomic instability, and tumor kinetics. Cancer Res 61: 538–549.VG GorgoulisP. ZacharatosG. MariatosT. LiloglouS. Kokotas2001Deregulated Epression of c-mos in non-small cell lung carcinomas: Relationship with p53 status, genomic instability, and tumor kinetics.Cancer Res61538549
- 103. Matsumoto S, Abe Y, Fujibuchi T, Takeuchi T, Kito K, et al. (2004) Characterization of a MAPKK-like protein kinase TOPK. Biochem Biophys Res Commun 325: 997–1004.S. MatsumotoY. AbeT. FujibuchiT. TakeuchiK. Kito2004Characterization of a MAPKK-like protein kinase TOPK.Biochem Biophys Res Commun3259971004
- 104. Jiang X, Takahashi N, Ando K, Otsuka T, Tetsuka T, et al. (2003) NF-κB p65 transactivation domain is involved in the NF-κB-inducing kinase pathway. Biochem Biophys Res Commun 301: 583–590.X. JiangN. TakahashiK. AndoT. OtsukaT. Tetsuka2003NF-κB p65 transactivation domain is involved in the NF-κB-inducing kinase pathway.Biochem Biophys Res Commun301583590
- 105. Sugimoto K, Ohata M, Miyoshi J, Ishizaki H, Tsuboi N, et al. (2004) A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced Il-12 production and Thr cell differentiation. J Clin Invest 114: 857–866.K. SugimotoM. OhataJ. MiyoshiH. IshizakiN. Tsuboi2004A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced Il-12 production and Thr cell differentiation.J Clin Invest114857866
- 106. Malinin NL, Boldin MP, Kovalenko AV, Wallach D (1997) MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature 385: 540–544.NL MalininMP BoldinAV KovalenkoD. Wallach1997MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1.Nature385540544
- 107. Vega FM, Sevilla A, Lazo PA (2004) p53 Stabilization and accumulation induced by human vaccinia-related kinase 1. Mol Cell Biol 24: 10366–10380.FM VegaA. SevillaPA Lazo2004p53 Stabilization and accumulation induced by human vaccinia-related kinase 1.Mol Cell Biol241036610380
- 108. Zhang O, Yoshimatsu Y, Hildebrand J, Frisch SM, Goodman G (2003) Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP Cell. 115. : 177–186.O. ZhangY. YoshimatsuJ. HildebrandSM FrischG. Goodman2003Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP Cell115177186
- 109. Zhanga D, Lib K, Erickson-Millerc CL, Weissd M, Wojchowski DM (2005) DYRK gene structure and erythroid-restricted features of DYRK3 gene expression Genomics. 85. : 117–130.D. ZhangaK. LibCL Erickson-MillercM. WeissdDM Wojchowski2005DYRK gene structure and erythroid-restricted features of DYRK3 gene expression Genomics85117130
- 110. Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, et al. (1998) SRPK2: A differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells. J Cell Biol 140: 737–750.HY WangW. LinJA DyckJM YeakleyZ. Songyang1998SRPK2: A differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells.J Cell Biol140737750
- 111. Rykx A, Kimpe LD, Mikhalap S, Vantus T, Seufferlein T, et al. (2003) Protein kinase D: A family affair. FEBS Lett 546: 81–86.A. RykxLD KimpeS. MikhalapT. VantusT. Seufferlein2003Protein kinase D: A family affair.FEBS Lett5468186
- 112. Xin X, Ferraro F, Bäck N, Eipper BA, Mains RE (2004) Cdk5 and Trio modulate endocrine cell exocytosis. J Cell Sci 117: 4739–4746.X. XinF. FerraroN. BäckBA EipperRE Mains2004Cdk5 and Trio modulate endocrine cell exocytosis.J Cell Sci11747394746
- 113. Inbal B, Shani G, Cohen O, Kissil JL, Kimchi A (2000) Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis. Mol Cell Biol 20: 1044–1054.B. InbalG. ShaniO. CohenJL KissilA. Kimchi2000Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis.Mol Cell Biol2010441054
- 114. Shohat G, Shani G, Eisenstein M, Kimchi A (2002) The DAP-kinase family of proteins: Study of a novel group of calcium-regulated death-promoting kinases. Biochim Biophys Acta 1600: 45–50.G. ShohatG. ShaniM. EisensteinA. Kimchi2002The DAP-kinase family of proteins: Study of a novel group of calcium-regulated death-promoting kinases.Biochim Biophys Acta16004550
- 115. Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, et al. (2001) The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol Cell 7: 1307–1319.P. KarumanO. GozaniRD OdzeXC ZhouH. Zhu2001The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death.Mol Cell713071319
- 116. Boehm M, Yoshimoto T, Crook MF, Nallamshetty S, True A, et al. (2002) A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression. EMBO J 21: 3390–3401.M. BoehmT. YoshimotoMF CrookS. NallamshettyA. True2002A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression.EMBO J2133903401
- 117. Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, et al. (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44: 595–600.C. Paisan-RuizS. JainEW EvansWP GilksJ. Simon2004Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease.Neuron44595600
- 118. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, et al. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44: 601–607.A. ZimprichS. BiskupP. LeitnerP. LichtnerM. Farrer2004Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.Neuron44601607
- 119. Becraft PW, Stinard PS, McCarty DR (1996) CRINKLY4: A TNFR-like receptor kinase involved in maize epidermal differentiation. Science 273: 1406–1409.PW BecraftPS StinardDR McCarty1996CRINKLY4: A TNFR-like receptor kinase involved in maize epidermal differentiation.Science27314061409
- 120. Lee JH, Takei K, Sakakibara H, Cho HS, Kim DM, et al. (2003) CHRK1, a chitinase-related receptor-like kinase, plays a role in plant development and cytokinin homeostasis in tobacco. Plant Mol Biol 53: 877–890.JH LeeK. TakeiH. SakakibaraHS ChoDM Kim2003CHRK1, a chitinase-related receptor-like kinase, plays a role in plant development and cytokinin homeostasis in tobacco.Plant Mol Biol53877890
- 121. Chen K, Fan B, Du L, Chen Z (2004) Activation of hypersensitive cell death by pathogen-induced receptor-like protein kinases from Arabidopsis. Plant Mol Biol 56: 271–283.K. ChenB. FanL. DuZ. Chen2004Activation of hypersensitive cell death by pathogen-induced receptor-like protein kinases from Arabidopsis.Plant Mol Biol56271283
- 122. Du L, Chen Z (2000) Identification of genes encoding receptor-like protein kinases as possible targets of pathogen- and salicyclic acid-induced WRKY DNA-binding proteins in Arabidopsis. Plant J 24: 837–847.L. DuZ. Chen2000Identification of genes encoding receptor-like protein kinases as possible targets of pathogen- and salicyclic acid-induced WRKY DNA-binding proteins in Arabidopsis.Plant J24837847
- 123. Zuo K, Zhao J, Wang J, Sun X, Tang K (2004) Molecular cloning and characterization of GhleckRK, a novel kinase gene with lectin-like domain from Gossypium hirsutum. DNA Seq 15: 58–65.K. ZuoJ. ZhaoJ. WangX. SunK. Tang2004Molecular cloning and characterization of GhleckRK, a novel kinase gene with lectin-like domain from Gossypium hirsutum.DNA Seq155865
- 124. Robatzek S, Somssich IE (2002) Targets of AtWRKY6 regulation during plant senescence and pathogen defense. Genes Dev 16: 1139–1149.S. RobatzekIE Somssich2002Targets of AtWRKY6 regulation during plant senescence and pathogen defense.Genes Dev1611391149
- 125. Stracke S, Kistner C, Yoshida S, Mulder L, Sato S, et al. (2002) A plant receptor-like kinase required for both bacterial and fungal symbiosis. Nature 417: 959–962.S. StrackeC. KistnerS. YoshidaL. MulderS. Sato2002A plant receptor-like kinase required for both bacterial and fungal symbiosis.Nature417959962
- 126. Endre G, Kereszt A, Kevei Z, Mihacea S, Kaló P, et al. (2002) A receptor kinase gene regulating symbiotic nodule development. Nature 417: 962–966.G. EndreA. KeresztZ. KeveiS. MihaceaP. Kaló2002A receptor kinase gene regulating symbiotic nodule development.Nature417962966
- 127. Li J, Wen J, Lease KA, Doke JT, Tax FE, et al. (2002) BAK1, an Arabidopsis LRR receptor-like protein kinase, interacts with BRI1 and modulates brassinosteroid signaling. Cell 110: 213–222.J. LiJ. WenKA LeaseJT DokeFE Tax2002BAK1, an Arabidopsis LRR receptor-like protein kinase, interacts with BRI1 and modulates brassinosteroid signaling.Cell110213222
- 128. Kwak S, Shen R, Schiefelbein J (2005) Positional signaling mediated by a receptor-like kinase in Arabidopsis. Science 307: 1111–1113.S. KwakR. ShenJ. Schiefelbein2005Positional signaling mediated by a receptor-like kinase in Arabidopsis.Science30711111113
- 129. Takahashi T, Mu JH, Gasch A, Chua NH (1998) Identification by PCR of receptor-like protein kinases from Arabidopsis flowers. Plant Mol Biol 37: 587–596.T. TakahashiJH MuA. GaschNH Chua1998Identification by PCR of receptor-like protein kinases from Arabidopsis flowers.Plant Mol Biol37587596
- 130. Li J, Chory J (1997) A putative leucine-rich repeat receptor kinase involved in brassinosteroid signal transduction. Cell 90: 825–827.J. LiJ. Chory1997A putative leucine-rich repeat receptor kinase involved in brassinosteroid signal transduction.Cell90825827
- 131. Scheer JM, Ryan CA Jr (2002) The systemin receptor SR160 from Lycopersicon peruvianum is a member of the LRR receptor kinase family. Proc Natl Acad Sci U S A 99: 9585–9590.JM ScheerCA Ryan Jr2002The systemin receptor SR160 from Lycopersicon peruvianum is a member of the LRR receptor kinase family.Proc Natl Acad Sci U S A9995859590
- 132. Caño-Delgado A, Yin Y, Yu C, Vafeados D, Mora-García S, et al. (2004) BRL1 and BRL3 are novel brassinosteroid receptors that function in vascular differentiation in Arabidopsis. Development 131: 5341–5351.A. Caño-DelgadoY. YinC. YuD. VafeadosS. Mora-García2004BRL1 and BRL3 are novel brassinosteroid receptors that function in vascular differentiation in Arabidopsis.Development13153415351
- 133. Zhao D, Wang G, Speal B, Ma H (2002) The EXCESS MICROSPOROCYTES1 gene encodes a putative leucine-rich repeat receptor protein kinase that controls somatic and reproductive cell fates in the Arabidopsis anther. Genes Dev 16: 2021–2031.D. ZhaoG. WangB. SpealH. Ma2002The EXCESS MICROSPOROCYTES1 gene encodes a putative leucine-rich repeat receptor protein kinase that controls somatic and reproductive cell fates in the Arabidopsis anther.Genes Dev1620212031
- 134. Matsubayashi Y, Ogawa M, Morita A, Sakagami Y (2002) An LRR receptor kinase involved in perception of a peptide plant hormone, phytosulfokine. Science 296: 1470–1472.Y. MatsubayashiM. OgawaA. MoritaY. Sakagami2002An LRR receptor kinase involved in perception of a peptide plant hormone, phytosulfokine.Science29614701472
- 135. Clark SE, Williams RW, Meyerowitz EM (1997) The CLAVATA1 gene encodes a putative receptor kinase that controls shoot and floral meristem size in Arabidopsis. Cell 89: 575–585.SE ClarkRW WilliamsEM Meyerowitz1997The CLAVATA1 gene encodes a putative receptor kinase that controls shoot and floral meristem size in Arabidopsis.Cell89575585
- 136. Bommert P, Lunde C, Nardmann J, Vollbrecht E, Running M, et al. (2005) Thick tassel dwarf1 encodes a putative maize ortholog of the Arabidopsis CLAVATA1 leucine-rich repeat receptor-like kinase. Development 132: 1235–1245.P. BommertC. LundeJ. NardmannE. VollbrechtM. Running2005Thick tassel dwarf1 encodes a putative maize ortholog of the Arabidopsis CLAVATA1 leucine-rich repeat receptor-like kinase.Development13212351245
- 137. Suzaki T, Sato M, Ashikari M, Miyoshi M, Nagato Y, et al. (2004) The gene FLORAL ORGAN NUMBER1 regulates floral meristem size in rice and encodes a leucine-rich repeat receptor kinase orthologous to Arabidopsis CLAVATA1. Development 131: 5649–5657.T. SuzakiM. SatoM. AshikariM. MiyoshiY. Nagato2004The gene FLORAL ORGAN NUMBER1 regulates floral meristem size in rice and encodes a leucine-rich repeat receptor kinase orthologous to Arabidopsis CLAVATA1.Development13156495657
- 138. Jinn T, Stone JM, Walker JC (2000) HAESA, an Arabidopsis leucine-rich repeat receptor kinase, controls floral organ abscission. Genes Dev 14: 108–117.T. JinnJM StoneJC Walker2000HAESA, an Arabidopsis leucine-rich repeat receptor kinase, controls floral organ abscission.Genes Dev14108117
- 139. Torii KU, Mitsukawa N, Oosumi T, Matsuura Y, Yokoyama R, et al. (1996) The Arabidopsis ERECTA gene encodes a putative receptor protein kinase with extracellular leucine-rich repeats. Plant Cell 8: 735–746.KU ToriiN. MitsukawaT. OosumiY. MatsuuraR. Yokoyama1996The Arabidopsis ERECTA gene encodes a putative receptor protein kinase with extracellular leucine-rich repeats.Plant Cell8735746
- 140. Osakabe Y, Maruyama K, Seka M, Satou M, Shinozaki K, et al. (2005) Leucine-rich repeat receptor-like kinase1 is a key membrane-bound regulator of abscisic acid early signaling in Arabidopsis. Plant Cell 17: 1105–1119.Y. OsakabeK. MaruyamaM. SekaM. SatouK. Shinozaki2005Leucine-rich repeat receptor-like kinase1 is a key membrane-bound regulator of abscisic acid early signaling in Arabidopsis.Plant Cell1711051119
- 141. Limpens E, Franken C, Smit P, Willemse J, Bisseling T, et al. (2003) LysM domain receptor kinases regulating rhizobial Nod factor-induced infection. Science 302: 630–633.E. LimpensC. FrankenP. SmitJ. WillemseT. Bisseling2003LysM domain receptor kinases regulating rhizobial Nod factor-induced infection.Science302630633
- 142. Silva NF, Goring DR (2002) The proline-rich, extension-like receptor kinase-1 (PERK1) gene is rapidly induced by wounding. Plant Mol Biol 50: 667–685.NF SilvaDR Goring2002The proline-rich, extension-like receptor kinase-1 (PERK1) gene is rapidly induced by wounding.Plant Mol Biol50667685
- 143. Stein JC, Howlett B, Boyes DC, Nasrallah ME, Nasrallah JB (1991) Molecular cloning of a putative receptor protein kinase gene encoded at the self-incompatibility locus of Brassica oleracea. Proc Natl Acad Sci U S A 88: 8816–8820.JC SteinB. HowlettDC BoyesME NasrallahJB Nasrallah1991Molecular cloning of a putative receptor protein kinase gene encoded at the self-incompatibility locus of Brassica oleracea.Proc Natl Acad Sci U S A8888168820
- 144. Pastuglia M, Swarup R, Rocher A, Saindrenan P, Roby D, et al. (2002) Comparison of the expression patterns of two small gene families of S gene family receptor kinase genes during the defence response in Brassica oleracea and Arabidopsis thaliana. Gene 282: 215–225.M. PastugliaR. SwarupA. RocherP. SaindrenanD. Roby2002Comparison of the expression patterns of two small gene families of S gene family receptor kinase genes during the defence response in Brassica oleracea and Arabidopsis thaliana.Gene282215225
- 145. He ZH, He D, Kohorn BD (1998) Requirement for the induced expression of a cell wall associated receptor kinase for survival during the pathogen response. Plant J 14: 55–63.ZH HeD. HeBD Kohorn1998Requirement for the induced expression of a cell wall associated receptor kinase for survival during the pathogen response.Plant J145563
- 146. Sivaguru M, Ezaki B, He ZH, Tong H, Osawa H, et al. (2003) Aluminum-induced gene expression and protein localization of a cell wall-associated receptor kinase in Arabidopsis. Plant Physiol 132: 2256–2266.M. SivaguruB. EzakiZH HeH. TongH. Osawa2003Aluminum-induced gene expression and protein localization of a cell wall-associated receptor kinase in Arabidopsis.Plant Physiol13222562266
- 147. Lally D, Ingmire P, Tong HY, He ZH (2001) Antisense expression of a cell wall-associated protein kinase, WAK4, inhibits cell elongation and alters morphology. Plant Cell 13: 1317–1331.D. LallyP. IngmireHY TongZH He2001Antisense expression of a cell wall-associated protein kinase, WAK4, inhibits cell elongation and alters morphology.Plant Cell1313171331
- 148. Verica JA, Chae L, Tong H, Ingmire P, He Z (2003) Tissue-specific and developmentally regulated expression of a cluster of tandemly arrayed cell wall-associated kinase-like kinase genes in Arabidopsis. Plant Physiol 133: 1732–1746.JA VericaL. ChaeH. TongP. IngmireZ. He2003Tissue-specific and developmentally regulated expression of a cluster of tandemly arrayed cell wall-associated kinase-like kinase genes in Arabidopsis.Plant Physiol13317321746
- 149. Mu J, Lee H, Kao T (1994) Characterization of a pollen-expressed receptor-like kinase gene of Petunia inflate and the activity of its encoded kinase. Plant Cell 6: 709–721.J. MuH. LeeT. Kao1994Characterization of a pollen-expressed receptor-like kinase gene of Petunia inflate and the activity of its encoded kinase.Plant Cell6709721
- 150. Li Y, Sun J, Xia G (2005) Cloning and characterization of a gene for an LRR receptor-like protein kinase associated with cotton fiber development. Mol Genet Genom 273: 217–224.Y. LiJ. SunG. Xia2005Cloning and characterization of a gene for an LRR receptor-like protein kinase associated with cotton fiber development.Mol Genet Genom273217224
- 151. Hattan J, Kanamoto H, Takemura M, Yokota A, Kohchi T (2004) Molecular characterization of the cytoplasmic interacting protein of the receptor kinase IRK expressed in the inflorescence and root apices of Arabidopsis. Biosci Biotechnol Biochem 68: 2598–2606.J. HattanH. KanamotoM. TakemuraA. YokotaT. Kohchi2004Molecular characterization of the cytoplasmic interacting protein of the receptor kinase IRK expressed in the inflorescence and root apices of Arabidopsis.Biosci Biotechnol Biochem6825982606