The alpha v beta 3 integrin associates with a 190-kDa protein that is phosphorylated on tyrosine in response to platelet-derived growth factor.
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.
Bartfeld
N S
NS
R. W. Johnson Pharmaceutical Research Institute, San Diego, California 92121.
Pasquale
E B
EB
Geltosky
J E
JE
Languino
L R
LR
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D004591:Electrophoresis, Polyacrylamide Gel; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D016024:Receptors, Cytoadhesin / Q000378:metabolism*; D019030:Receptors, Vitronectin; D014443:Tyrosine / Q000378:metabolism
D016023:Integrins; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D014443:Tyrosine