CLUSTERING OF THE PLATELET FC-GAMMA RECEPTOR INDUCES NONCOVALENT ASSOCIATION WITH THE TYROSINE KINASE P72(SYK)

The Fc receptor for IgG in platelets was identified as the integral me mbrane isoform encoded by the Fc gamma RIIA gene. Functional analysis of this molecule determined that activated Fc gamma RIIA is tyrosine p hosphorylated and that activation induced the physical association wit h the protein tyrosine kinase p72(syk). Other tyrosine-phosphorylated molecules also co-immunoadsorbed with the activated receptor. Tyrosine kinase activity co-immuno-adsorbing with the platelet Fc gamma R was enhanced upon activation and specifically induced the phosphorylation, on tyrosine residues, of a physically associated 72-kDa protein. Thes e data support a model of Fc gamma receptor-mediated platelet activati on where signal is transduced through inducible association of the tyr osine kinase p72(syk) with the low affinity Fc gamma receptor. Thrombi n, a potent platelet agonist, has been shown to up-regulate the activi ty of the tyrosine kinase p72(syk) in platelets, Consequently, our fin dings identify a second pathway by which p72(syk) in activated in plat elets.