Fig. 6

Model for the activation of C3G. Activation of C3G is a three-step process. Initial recruitment relies on the interaction of CrkL with the P1 and P2 sites. Translocation to the plasma membrane is independent of the activation of C3G. The second step is the priming of C3G by phosphorylation in tyrosine residues by Src-family kinases (SFKs) or other kinases such as Abl. Phosphorylation alone is insufficient for activation. The third step is the actual activation, which occurs when CrkL interacts with the P3 and P4 sites in phosphorylated C3G. CrkL stabilizes an open state of pC3G in which the autoinhibitory interaction between the AIR and Cdc25HD is prevented, unleashing the GEF activity of the Cdc25HD. Activation is likely to be reverted, among other mechanisms, through the action of tyrosine phosphatases, which would result in the dissociation of CrkL from the P3 activation site and the diffusion of inactive CrkL/C3G complexes to the cytoplasm