PAXILLIN, A TYROSINE-PHOSPHORYLATED FOCAL ADHESION-ASSOCIATED PROTEIN BINDS TO THE CARBOXYL-TERMINAL DOMAIN OF FOCAL ADHESION KINASE

Focal adhesion kinase (pp125(FAK) or FAK) and paxillin colocalize with integrins in structures called focal adhesions. pp125(FAK) plays an important role in the transmission of integrin-induced cytoplasmic signals. Paxillin has also been implicated in cell signaling by virtue of its association with the protein tyrosine kinases pp60(src) and Csk (C-terminal Src kinase) as well as with the adapter/oncoprotein p47(gag-crk). In this report we show that endogenous pp125(FAK) and paxillin form a stable complex both in vivo and in vitro and that this interaction is direct, requiring only pp125(FAK) and paxillin. The paxillin binding site on pp125(FAk) has been localized to the carboxy-terminal 148 residues of pp125(FAK) but appears to be distinct from the previously identified focal adhesion-targeting sequence also present in the carboxy-terminal domain of pp125(FAK). The interaction of paxillin and pp125(FAK) is independent of the adhesion of cells to the extracellular matrix, as the association can be detected in suspension cells as well as those attached to fibronectin.