This proposal will examine the structure and function of a 40 kDa protein in platelets which we believe to be the alpha subunit of a guanine nucleotide-binding regulatory protein or G protein. Based upon our recent studies, this protein has several novel properties. First, it is phosphorylated during platelet activation, apparently by protein kinase C. Second, it is immunologically cross-reactive with G(z-alpha), a putative alpha subunit that has been cloned from two non-platelet cDNA libraries, but not yet isolated. Third, in contrast to the other G proteins which have been a focus for platelet research, it is neither ADP-ribosylated by pertussis toxin nor recognized by antisera that are specific for known pertussis toxin-sensitive G proteins, such as G(i-alpha). Even though G(z- alpha) is not known to be a substrate for protein kinase C, we have provisionally named the platelet protein """"""""G(z-alpha)(plt)"""""""" in acknowledgement of the immunologic cross-reactivity of the two proteins. The goal of our studies will be to understand the structure and biology of G(z-alpha)(plt). Specifically, we will: (1) determine the identity of G(z- alpha)(plt) and define its relationship to G(z-alpha), (2) identify the sites at which G(z-alpha)(plt) is phosphorylated, (3) determine the biochemical consequences of phosphorylation and (4) define the role of G(z- alpha)(plt) in platelet function.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Hematology Subcommittee 2 (HEM)
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University of Pennsylvania
Schools of Medicine
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