Phosphorylation of tyrosine 90 in SH3 domain is a new regulatory switch controlling Src kinase.

ABSTRACT: The activation of Src kinase in cells is strictly controlled by intramolecular inhibitory interactions mediated by SH3 and SH2 domains. They impose structural constraints on the kinase domain holding it in a catalytically non-permissive state. The transition between inactive and active conformation is known to be largely regulated by the phosphorylation state of key tyrosines 416 and 527. Here, we identified that phosphorylation of tyrosine 90 reduces binding affinity of the SH3 domain to its interacting partners, opens the Src structure, and renders Src catalytically active. This is accompanied by an increased affinity to the plasma membrane, decreased membrane motility, and slower diffusion from focal adhesions. Phosphorylation of tyrosine 90 controlling SH3-medited intramolecular inhibi

SUBMITTER: Koudelkova L 

PROVIDER: S-EPMC10361714 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature