Author/Authors :
Xiaojing Tang، نويسنده , , Stephen Orlicky، نويسنده , , Zhenyuan Lin، نويسنده , , Andrew Willems، نويسنده , , Dante Neculai، نويسنده , , Derek Ceccarelli، نويسنده , , Frank Mercurio، نويسنده , , Brian H. Shilton، نويسنده , , Frank Sicheri، نويسنده , , Mike Tyers، نويسنده ,
Abstract :
which the N-terminal FERM domain directly binds the kinase domain, blocking access to the catalytic cleft and protecting the FAK activation loop from Src phosphorylation. Additionally, the FERM domain sequesters the Tyr397 autophosphorylation and Src recruitment site, which lies in the linker connecting the FERM and kinase domains. The active phosphorylated FAK kinase adopts a conformation that is immune to FERM inhibition. Our biochemical and structural analysis shows how the architecture of autoinhibited FAK orchestrates an activation sequence of FERM domain displacement, linker autophosphorylation, Src recruitment, and full catalytic activation.
