MOLECULAR CLONING OF HUMAN PLATELET GLYCOPROTEIN IB

这项研究涉及动脉中的血小板粘附，重点是 粘附受体，血小板糖蛋白（GP）Ib。长期 目的是表征基因、遗传缺陷、转录本和 与GP Ib相关的多肽。 循环血小板的功能是内皮细胞的监视器 粘附在暴露的内皮下区域。 在 血管损伤部位，血小板粘附或“粘连”启动 正常的血小板栓形成阻止失血。 部位的 然而，血管疾病，血小板粘附引起异常血栓形成 导致心脏病和中风 在动脉循环中， 血小板表面糖蛋白Ib作为粘附的接触点 通过结合血管性血友病因子并将其作为血管 面 另外两种表面糖蛋白GP V和GP IX与GP相关， Ib通过共同的结构元件（富含亮氨酸的糖蛋白 序列）和常见的先天性缺陷状态（Bernard-Soulier 综合征）。 GP Ib和GP IX在GP Ib-IX复合物中直接缔合。 源于分散在不同的基因组上的四个基因（lb α/lb β/V/IX）， 染色体，三种蛋白质，GP lb/V/IX似乎协同工作， 产生功能性表面GP Ib受体。 该提案提出，“什么关系协调lb/V/IX 系统？”“基因有共同的结构吗，特别是启动子？" “是否有一种共同的机制调节基因表达？“”一个基因缺陷 会导致先天性缺乏三种表面GP吗““能 转染的cDNA产生成熟的表面GP Ib受体？" 具体目标和实验方法 1.人血小板糖蛋白cDNA的克隆与鉴定 诉 2.克隆和表征编码糖蛋白Ibbeta，V， 和IX. 3.描述两例Bernard Soulier的遗传缺陷 综合征 4.表征lbalpha、lbbeta、V， IX基因。 5.使用转染的cDNA评估Ibalpha的结构和功能。

The research deals with platelet adhesion in arteries, focusing on an adhesion receptor, platelet glycoprotein (GP) lb. The long-term objective is to characterize genes, genetic defects, transcripts and polypeptides that relate to GP lb. Circulating platelets function as monitors of the endothelial lining of blood vessels, sticking to areas with exposed subendothelium. At sites of vascular injury, platelet adhesion or "sticking" initiates normal platelet plug formation that stops blood loss. At sites of vascular disease, however, platelet adhesion sets off abnormal thrombosis that leads to heart attacks and strokes. In the arterial circulation, platelet surface glycoprotein lb serves as the contact point for adhesion by binding von Willebrand factor and using it as a link to the vascular surface. Two other surface glycoproteins, GP V and GP IX, are related to GP lb through common structural elements (leucine-rich glycoprotein sequences) and a common congenital deficiency state (Bernard-Soulier syndrome). GP lb and GP IX associate directly in the GP lb-IX complex. Stemming from four genes (lb alpha/lb beta/V/IX) dispersed on separate chromosomes, the three proteins, GP lb/V/IX appear to work in concert to produce a functional surface GP lb receptor. This proposal asks, "What relationships coordinate the lb/V/IX system?" "Do the genes share common structures, particularly promoters?" "Does a common mechanism regulate gene expression?" "Can one gene defect cause a congenital deficiency of the three surface GP's?" "Can transfected cDNAs produce a mature surface GP lb receptor?" Specific Aims and Experimental Approach 1. Clone and characterize the cDNA encoding human platelet glycoprotein V. 2. Clone and characterize genomic DNA encoding glycoproteins Ibbeta, V, and IX. 3. Characterize the genetic defect in two cases of Bernard Soulier syndrome. 4. Characterize the transcriptional response of the lbalpha, lbbeta, V, IX genes. 5. Assess the structure and function of lbalpha using transfected cDNAs.