SIGNALING THROUGH FOCAL ADHESION KINASE

Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase i mplicated in controlling cellular responses to the engagement of cell- surface integrins, including cell spreading and migration, survival an d proliferation. Aberrant FAK signaling may contribute to the process of cell transformation by certain oncoproteins, including v-Src. Progr ess toward elucidating the events leading to FAK activation following integrin-mediated cell adhesion, as well as events downstream of FAK, has come through the identification of FAK phosphorylation sites and i nteracting proteins. A signaling partnership is formed between FAK and Src-family kinases, reading to tyrosine phosphorylation of FAK and as sociated 'docking' proteins Cas and paxillin. Subsequent recruitment o f proteins containing Src homology 2 domains, including Grb2 and c-Crk , to the complex is likely to trigger adhesion-induced cellular respon ses, including changes to the actin cytoskeleton and activation of the Pas-MAP kinase pathway.