Identification and functional analysis of a new phosphorylation site (Y398) in the SH3 domain of Abi-1

Abstract: Abi-1 is an adaptor protein for Abelson kinase (c-Abl), and Abi-1 promotes the Abl-mediated phosphorylation of Mammalian Enabled (Mena) by binding both c-Abl and Mena. Here, we identified a new phosphorylation site (Y398) in the SH3 domain of Abi-1, and disruption of Y398, combined with the previously identified phosphorylation site Y213, significantly weakens the binding of Abi-1 to c-Abl. The SH3 domain of Abi-1 and the proline-rich domain of c-Abl are involved in this interaction. Abi-1 phosphorylation at both sites stimulates the phosphorylation of Mena through the activation of c-Abl kinase. The phosphorylation of Abi-1 also plays a role in enhancing the adhesion of Bcr-Abl-transformed leukemic cells. Structured summary of protein interactions: Abi1 physically interacts with c-Abl by pull down (View Interaction 1, 2) c-Abl physically interacts with Abi1 by anti bait coimmunoprecipitation (View Interaction 1, 2) c-Abl physically interacts with Abi1 by pull down (View interaction) [Copyright &y& Elsevier]