CHARACTERIZATION OF A NOVEL G PROTEIN IN HUMAN PLATELETS

这项提案将研究40 kDa蛋白质的结构和功能 在我们认为是鸟嘌呤的阿尔法亚单位的血小板中 核苷酸结合调节蛋白或G蛋白。根据我们最近的调查 研究表明，这种蛋白质具有几种新的特性。首先，它是 在血小板活化过程中被磷酸化，显然是由蛋白激酶C引起的。 其次，它与G(z-α)有免疫交叉反应，G(z-α)是一种假定的 从两个非血小板基因文库中克隆的α亚基， 但还没有被孤立。第三，与其他G蛋白不同的是 一直是血小板研究的焦点，它既不是ADP-核糖化的 百日咳毒素不能被已知的特异性抗血清识别 百日咳毒素敏感型G蛋白，如G(I-α)。即使G(z- Alpha)是蛋白激酶C的底物是未知的，我们有 将血小板蛋白暂命名为“G(z-α)(PLT)” 承认这两种蛋白质的免疫交叉反应。 我们研究的目标将是了解细胞的结构和生物学 G(z-α)(PLT)。具体来说，我们将：(1)确定G(z-)的身份。 Alpha)(PLT)并定义其与G(z-Alpha)的关系，(2)标识 G(z-α)(PLT)被磷酸化的位置，(3)决定 磷酸化的生化后果和(4)确定G(z- Alpha)(PLT)与血小板功能有关。

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.