The v-Src SH3 Domain Facilitates a Cell Adhesion-independent Association with Focal Adhesion Kinase*

Integrins facilitate cell attachment to the extracellu-lar matrix, and these interactions generate cell survival, proliferation, and motility signals. Integrin signals are relayed in part by focal adhesion kinase (FAK) activa-tion and the formation of a transient signaling complex initiated by Src homology 2 (SH2)-dependent binding of Src family protein-tyrosine kinases to the FAK Tyr-397 autophosphorylation site. Here we show that in viral Src (v-Src)-transformed NIH3T3 fibroblasts, an adhesion-in-dependent FAK-Src signaling complex occurs. Co-ex-pression studies in human 293T cells showed that v-Src could associate with and phosphorylate a Phe-397 FAK mutant at Tyr-925 promoting Grb2 binding to FAK in suspended cells. In vitro, glutathione S-transferase fu-sion proteins of the v-Src SH3 but not c-Src SH3 domai