Inducible tyrosine phosphorylation of the beta(3) integrin requires the alpha(v) integrin cytoplasmic tail

We have found that the integrin pa chain can be phosphorylated on tyrosine residues in K562 cells transfected with alpha(v) beta(3). Tyrosine phosphorylation of the beta(3) cytoplasmic tail is induced by adhesion to alpha(v) beta(3)-specific ligand or antibody or by incubation in manganese-containing buffer, Under the same conditions, beta(5) does not become tyrosine-phosphorylated in K562 transfected with alpha(v) beta(5). Phosphorylation of the beta(3) subunit requires the simultaneous presence of the alpha(v) subunit cytoplasmic tail, because neither the alpha(IIb) subunit nor a truncated alpha(v) subunit is sufficient to permit phosphorylation of beta(3), when coexpressed as a heterodimer with beta(3). Finally, tyrosine phosphorylation of the beta(3) cytoplasmic tail occurs on both human and murine beta(3) and is inducible in the ovarian carcinoma OV10 as well, independent of expression of integrin-associated protein (CD47), Tyrosine phosphorylation of the beta(3) integrin subunit facilitates association of Grb-2, an adaptor protein leading to activation of the Ras signaling pathway, and may contribute to the unique functional and signaling capabilities of alpha(v) beta(3).