Molecular Playground/FAK: Difference between revisions

<applet load='1MP8' size='400' color='black' frame='true' align='right' caption='Crystal structure of Focal Adhesion Kinase (FAK) kinase domain complex with ADP [[1mp8]]'/>

<scene name='User:Dannielle_Ryman/Sandbox_1/Fak_solution/3'>NMR solution structure of the focal adhesion targeting domain of focal adhesion kinase in complex with a paxillin LD peptide: evidence for a two-site binding model.</scene>Focal adhesion kinase (FAK) contains a FERM (protein 4.1, ezrin, radixin and moesin homology) domain, a kinase domain and a focal adhesion targeting (FAT) domain. The FAT domain recruits FAK to focal contacts by associating with integrin-associated proteins such as talin and paxillin. It also links FAK to the activation of Rho GTPases by binding to guanine nucleotide-exchange factors (GEFs) such as p190 RhoGEF. FAK contains three proline-rich regions (PRR1–3), which bind Src-homology-3 (SH3) domain-containing proteins such as p130Cas, the GTPase regulator associated with FAK (GRAF) and the Arf-GTPase-activating protein ASAP1. FAK is phosphorylated (P) on several tyrosine residues, including Tyr397, 407, 576, 577, 861 and 925. Tyrosine phosphorylation on Tyr397 creates a Src-homology-2 (SH2) binding site for Src, phospholipase Cgamma (PLCgamma), suppressor of cytokine signalling (SOCS), growth-factor-receptor-bound protein 7 (GRB7), the Shc adaptor protein, p120 RasGAP and the p85 subunit of phosphatidylinositol 3-kinase (PI3K). Phosphorylation of Tyr576 and Tyr577 within the kinase domain is required for maximal FAK catalytic activity, whereas the binding of FAK-family interacting protein of 200 kDa (FIP200) to the kinase region inhibits FAK catalytic activity. FAK phosphorylation at Tyr925 creates a binding site for GRB2.<scene name='User:Dannielle_Ryman/Sandbox_1/Fak2/2'>Crystal Structure of Focal Adhesion Kinase Domain with 2 molecules in the Asymmetric Unit Complexed with ADP and ATP</scene>

1. Noble, Molecular Biophysics, 2001