Figure 1.

The structure of Src and the regulation of its kinase activity. (A) Src consists of the SH1 (tyrosine kinase), SH2, SH3, and SH4 (unique) domains; the SH3–SH2 connector; the SH2–kinase linker; a C-terminal tail regulatory region; and two tyrosine sites (Tyr416 and Tyr527). (B) The regulation of Src activity depends on the phosphorylation of two tyrosine sites and intramolecular interactions among the domains. Normally, phosphorylated Tyr527 binds to the SH2 domain and the SH2–kinase linker binds to the SH3 domain, and these binding events result in the protection of the catalytic pocket of Tyr 416 in the kinase domain (SH1) from inappropriate phosphorylation. The dephosphorylation of Ty527 results in conformational change, unlocking the catalytic pocket of Tyr 416 and subsequently activating Src through the intramolecular autophosphorylation of Tyr416.