MOLECULAR CLONING OF HUMAN PLATELET GLYCOPROTEIN IB

这项研究涉及动脉中的血小板黏附，重点是 一种黏附受体--血小板糖蛋白(GP)1b。长期的 目的是描述基因、遗传缺陷、转录本和 与GP lb相关的多肽。 循环中的血小板是内皮细胞衬里的监控器 血管，粘在有裸露的内皮下层的区域。在… 血管损伤部位、血小板黏附或“粘连”起始物 正常的血小板阻塞形成，可以止血。在以下地点 然而，血管疾病，血小板黏附会引发异常血栓形成 这会导致心脏病发作和中风。在动脉循环中， 血小板表面糖蛋白lb是黏附的接触点 通过结合von Willebrand因子并将其作为连接血管的纽带 浮出水面。 另外两种表面糖蛋白GP V和GP IX与GP有关 通过常见的结构元素(富含亮氨酸的糖蛋白 序列)和常见的先天性缺陷状态(Bernard-Soulier 综合症)。GP lb和GP ix直接结合在GP lb-IX复合体中。 源于四个基因(Lbα/Lbβ/V/IX)分散在不同的 染色体，这三种蛋白质，GP Lb/V/IX似乎协同工作 产生一种功能性的表面GP lb受体。 这项提议问道：“是什么关系协调Lb/V/IX 系统？“这些基因有共同的结构吗，特别是启动子？” “有没有一种共同的机制来调节基因表达？”“一个基因会不会有缺陷 导致三面肌先天性缺陷？“”可以吗？ 转基因的cDNA能产生成熟的表面GP lb受体？ 具体目标和实验方法 1.人血小板膜糖蛋白编码基因的克隆与鉴定 五. 2.克隆和鉴定编码糖蛋白Ibbeta、V、 和IX。 3.描述两例Bernard Soulier的遗传缺陷 综合症。 4.鉴定lbalpha，lbbeta，V， IX基因。 5.利用转染的cDNAs对Lbalpha的结构和功能进行研究。

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.