Requirement of integrin beta(3) tyrosine 747 for beta(3) tyrosine phosphorylation and regulation of alpha(v)beta(3) avidity

Leukocytes and platelets require stimulation for optimal beta(3) integrin receptor function, whereas beta(3) function is constitutive in many other cells, The molecular mechanisms that enhance integrin function in stimulated hematopoietic cells are poorly understood. Phosphorylation of the beta(3) cytoplasmic tail is a recently described but prevalent phenomenon, with unknown effects on gp, function. Here, we show that mutation of the beta(3) cytoplasmic tail tyrosine 747 to phenylalanine (Y747F) prevents beta(3) tyrosine phosphorylation in two cell lines. Whereas this mutation has no effect on alpha(v) beta(3)-mediated adhesion in a cell with constitutive beta(3) function, it completely abolishes adhesion and clot retraction by a cell that requires stimulation for beta(3) function. Ligand-induced conformational change as detected by LIBS-1 antibody occurs normally in Y747F mutant alpha(v) beta(3). Thus, tyrosine 747 of beta(3) is required for stimulation of alpha(v) beta(3)-mediated adhesion, probably due to its phosphorylation, Because the motif in beta(3) required for tyrosine phosphorylation is shared by several integrin beta-chains, this maybe a conserved mechanism for regulation of integrin-dependent adhesion.