Crosstalk between the catalytic and regulatory domains allows bidirectional regulation of Src.

摘要: The catalytic activity of Src family tyrosine kinases is inhibited by intramolecular interactions between the regulatory SH3 and SH2 domains domain. In inactive state, critical alphaC-helix in domain positioned such that formation Glu 310-Lys 295 salt bridge precluded, Tyr 416 activation loop unphosphorylated, are unavailable for with other proteins. We found phosphorylation or mutation preceding activates increases accessibility ligands. Interaction a central component this system. Our data suggest bidirectional regulation mechanism which inhibit activity, controls availability domains. By mechanism, can be activated proteins phosphorylating changing conformation Once active, become less prone to regulation, implying positive feedback on their activity.