MOLECULAR CLONING OF HUMAN PLATELET GLYCOPROTEIN IB

这项拟议的研究旨在更好地了解血小板 粘附，其涉及血小板与 受伤血管的表面。 这种互动是一种启动 也是正常止血和异常凝血的关键步骤 导致心脏病发作和中风的过程，称为 冠状动脉和脑血栓形成。 具体地说，这项研究集中在三个血小板的复合物上， 血小板粘附所需的蛋白质。 这些蛋白质， 称为糖蛋白（GP）Ib、V和IX，存在于表面上 并与循环中的血小板特异性相互作用， 粘附蛋白，血管性血友病因子（vWF），成为 与血管壁相连 GPIb本身似乎起着主要作用 在与vWF结合和作为锚阻止 血管损伤部位的循环血小板。 GPIb的结构目前尚不清楚， 研究试图在其氨基酸水平上定义GPIb 序列并定义mRNA和基因的结构 GPIb的代码 通过分子克隆技术， 分离编码GPIb的cDNA， 表征了 此外，GPIb基因将在 根据大小、染色体位置、调节特征和 编码区。 GPIb与粘附蛋白结合的机制， vWF，以及其他“复合体”成员GPV和 GPIX未知。 GPIb与vWF的结合反应 将在一级氨基酸序列水平上进行研究 每一种蛋白质都有。 此外，GPV和GPIX都将 纯化的，它们对GPIb-vWF相互作用的贡献将 被定义。 这项研究可以提供深入了解血小板如何发挥作用， 正常和病理性凝血 这项工作还可以提供 了解缺乏GPIb的患者的遗传异常 复杂.

The proposed research seeks a better understanding of platelet adhesion which involves the interaction of platelets with the surface of an injured blood vessel. This interaction is an initiating and crucial step in normal hemostasis and in abnormal clotting processes that contribute to heart attacks and strokes, termed coronary and cerebral thromboses. Specifically, the research focuses on a complex of three platelet proteins that are required for platelet adhesion. These proteins, termed glycoprotein (GP) Ib, V, and IX, are present on the surface of human platelets and interact specifically with a circulating adhesive protein, von Willebrand factor (vWF), that becomes bound to the vessel wall. GPIb itself appears to play the major role in binding to vWF and in serving as an anchor to stop the circulating platelet at a site of vessel damage. The structure of GPIb is currently unknown, and the proposed research seeks to define GPIb at the level of its amino acid sequence and to define the structure of the mRNA(s) and gene(s) which code for GPIb. By means of molecular cloning techniques, the cDNA which codes for GPIb will be isolated and characterized. In addition, the GPIb gene(s) will be defined in terms of size, chromosomal location, regulatory features and coding regions. Both the mechanism by which GPIb binds to the adhesive protein, vWF, and the role of the other "complex" members, GPV and GPIX, are unknown. The binding reaction between GPIb and vWF will be studied at the level of the primary amino acid sequences involved in each protein. In addition, both GPV and GPIX will be purified and their contribution to the GPIb-vWF interaction will be defined. This research can provide insight into how platelets function in both normal and pathological clotting. The work can also provide insight into the genetic abnormality of patients who lack the GPIb complex.