Tyrosine phosphorylation of the  3 subunit of the major platelet integrin ␣ IIb  3 has been shown to occur during thrombin-induced platelet aggregation (1). We now show that a wide variety of platelet stimuli induced  3 tyrosine phosphorylation, but that this phosphorylation occurred only following platelet aggregation. Several lines of evidence suggest that the  3 cytoplasmic domain tyrosine residues and/or their phosphorylation function to mediate interactions between  3 integrins and cytoskeletal proteins. First, phospho- 3 was retained preferentially in a Triton X-100 insoluble cytoskeletal fraction of thrombin-aggregated platelets. Second, in vitro experiments show that the cytoskeletal protein, myosin, associated in a phosphotyrosine-dependent manner with a diphosphorylated peptide corresponding to residues 740 -762 of  3 . Third, mutation of both tyrosines in the  3 cytoplasmic domain to phenylalanines markedly reduced  3 -dependent fibrin clot retraction. Thus, our data indicate that platelet aggregation is both necessary and sufficient for  3 tyrosine phosphorylation, and this phosphorylation results in the physical linkage of ␣ IIb  3 to the cytoskeleton. We hypothesize that this linkage may involve direct binding of the phosphorylated integrin to the contractile protein myosin in order to mediate transmission of force to the fibrin clot during the process of clot retraction.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.