Mathematical model of early Reelin-induced Src family kinase-mediated signaling
Fig 3
Scheme of the monomer (A) and complex (B) signaling models.
In the monomer model variant (A), Dab1 is activated by tyrosine phosphorylation after binding of Reelin to the receptor. The initial phosphorylation of Dab1 initiates phosphorylation of SFKs, which results in a positive feedback. Subsequently, p-Dab1 induces activation of downstream targets, such as Akt. Signaling is negatively regulated by degradation of phosphorylated Dab1, which is further increased through the Reelin-dependent activation of SFKs. In the complex model (B), clusters of the lipoprotein receptors are formed. These bind the adaptor protein Dab1, which is phosphorylated by SFKs. As a feed-forward loop, SFKs activated in a p-Dab1/SFK complex can trans-phosphorylate other Dab1 proteins bound to the receptor complex. The pathway is regulated by ubiquitination and degradation of phosphorylated Dab1.