The association of focal adhesion kinase with a 200-kDa protein that is tyrosine phosphorylated in response to platelet-derived growth factor.

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase implicated in the signal transduction pathways initiated by integrins. However, we have previously found that platelet-derived growth factor (PDGF) could stimulate the association of FAK with phosphatidylinositol 3-kinase in NIH 3T3 cells [Chen, H.-C. & Guan, J.-L. (1994) J. Biol. Chem 269, 31229-31223], suggesting that FAK might participate in some of the cellular effects of the growth factors in modulating cell morphology and migration. In this report, we describe the association of FAK with a 200-kDa protein (pp200) that is tyrosine phosphorylated in response to PDGF stimulation in NIH 3T3 cells. Although the identity of pp200 is unknown at present, we have excluded the possibilities that it is the PDGF receptor beta, tension, talin, myosin or the guanosine-triophosphatase-activating-protein-associated p190 protein. Furthermore, we found that the tyrosine phosphorylation of FAK-associated pp200 upon PDGF stimulation is largely independent of cell adhesion or the integrity of the cytoskeleton. Therefore, pp200 and its interaction with FAK may also be involved in growth-factor-induced cellular effects such as the modulation of cell adhesion or cell migration via cytoskeletal reorganization or disruption of focal adhesions.