Functional Mechanisms and Roles of Adaptor Proteins in Abl-Regulated Cytoskeletal Actin Dynamics
Figure 4
Regulatory mechanism of Abl kinase activity by Abi and Crk. (a) Events leading to the activation of the Abl kinase activity after the interaction of Abl and Abi1 or Abi2 are schematically illustrated. The regulatory Y213 and Y398 in Abi1 and Y324 in Abi2 are indicated. Phosphorylated Y213 and Y398 in Abi1 are involved in the interaction with c-Abl through the SH2 and PR region of c-Abl, respectively. (b) Y221 and Y251 in CrkII are sites of phosphorylation by Abl after the interaction of Abl and CrkII. When Y221 is phosphorylated, it induces an “autoinhibition” through an intramolecular SH2-pTyr clamp and the suppression of Abl kinase activity, resulting in the disassembly of Crk-mediated signaling complexes and abrogation of Crk-mediated signaling. On the other hand, Y251 in the SH3 domain interacts with the SH2 domain of Abl and releases the latch and clamp structure of Abl, leading to the activation of Abl.
