The alpha v beta 3 integrin associates with a 190-kDa protein that is phosphorylated on tyrosine in response to...

Integrins are cell surface heterodimers that mediate cell adhesion to the extracellular matrix. We show that in mouse 3T3 fibroblasts the alpha v beta 3 integrin (vitronectin receptor) coprecipitates with a tyrosine-phosphorylated 190-kDa protein, as detected by antibodies to phosphotyrosine. Three different antibodies to the vitronectin receptor, all of which precipitate the alpha/beta complex, coprecipitated a 190-kDa protein. The three antibodies were raised against the purified placental vitronectin receptor, the platelet alpha IIb beta 3 integrin, and the cytoplasmic domain of the alpha v subunit. The association was specific for the vitronectin receptor, since an antibody to the alpha 5 beta 1 integrin (fibronectin receptor) did not coprecipitate any tyrosine-phosphorylated protein. The phosphorylation of the 190-kDa protein was observed only following cell activation by platelet-derived growth factor, which is known to stimulate tyrosine kinase activity and to modulate cell adhesion. Antibodies raised against the platelet-derived growth factor alpha and beta receptors (M(r) = 170,000 and 190,000, respectively) did not recognize the 190-kDa, integrin-associated phosphorylated protein. Occupancy of the vitronectin receptor by one of its ligands, vitronectin, resulted in an increased amount of tyrosine phosphorylation of the 190-kDa protein. Our data suggest that the association of tyrosine-phosphorylated proteins with integrins may play an important role in growth factor-mediated modulation of cell adhesion.