Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity
Figure 1
Structural organization of KIT.
Stem Cell Factor (SCF) binding on the extracellular domain of KIT induces dimerization. Upon activation, KIT is autophosphorylated at tyrosine residues (magenta balls) that act as binding sites for downstream signaling kinases/mediators. The location of KIT gain-of-function mutations is indicated by residue numbers. Residues V560 and D816 (red balls), positioned in the JMR and in the kinase domain of the cytoplasmic region, are associated with highly malignant cancers. JMR, juxta-membrane region; KD, kinase domain; KID, kinase insert domain.