PHOSPHORYLATION OF TYROSINE-397 IN FOCAL ADHESION KINASE IS REQUIRED FOR BINDING PHOSPHATIDYLINOSITOL 3-KINASE

We have shown previously that cell adhesion or platelet-derived growth factor (PDGF) promotes the in vivo association of focal adhesion kina se (FAK) with phosphatidylinositol (PI) 3-kinase. In vitro experiments indicated that this interaction was mediated by the p85 subunit of PI 3-kinase and dependent on the tyrosine phosphorylation of FAK. Here w e report data suggesting that the major autophosphorylation site of FA K (Tyr-397) is the binding site for the SH2 domains of p85 in vitro an d is also required for the association of FAK with PI 3-kinase in vivo . We also show that Tyr-397 is responsible for the increased FAK:PI 3- kinase association upon PDGF stimulation, implying that no additional site of FAK was involved in its binding to PI 3-kinase after PDGF stim ulation, Finally, me present evidence that the interaction of PI 3-kin ase with Tyr-397 of FAK stimulates its activity, Together, these resul ts suggest that FAK activation and autophosphorylation at Tyr-397 may lead to its association with PI 3-kinase through the SH2 domains of p8 5, which can subsequently activate PI 3-kinase during cell adhesion.