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PLATELET CYTOSKELETAL ASSEMBLY & FUNCTION

血小板细胞骨架组装

基本信息

批准号：
3347345
负责人：
ROGER C CARROLL
金额：
$ 6.8万
依托单位：
UNIVERSITY OF TENNESSEE KNOXVILLE
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-12-01 至 1990-06-30
项目状态：
已结题

项目摘要

The platelet response to physiologic stimuli mediating platelet aggregation at a wound site is crucial to hemostasis. This platelet response and its reversal by prostaglandin I2 are also likely to be important to the pathophysiology of atherosclerosis, thrombophlebitis, and stroke. The long-term objective of this project is to understand the regulation of platelet cytoskeletal assembly during activation (actin polymerization, myosin and actin-binding protein phosphorylation and interaction with actin filaments), reversal of activation-cytoskeletal assembly by PGI2 elevation of platelet cAMP, and the relationship of this cytoskeletal assembly/disassembly to the expression of surface membrane sites mediating activation, adhesion, and aggregation. Towards obtaining this objective, it is proposed to isolate actin-binding protein to determine if its interaction with actin is modified by its in situ phosphorylation by protein kinase C during activation and by cAMP-dependent kinase during the reversal or inhibition of activation-cytoskeletal assembly. Membrane glycoprotein- cytoskeletal complexes have been isolated from PGI2-inactivated platelets. It is proposed to determine whether these complexes are essential to platelet activation as regulated precursors of cytoskeletal assembly and whether the disruption of such complexes is the mechanism by which certain amphiphilic compounds inhibit platelet activation-cytoskeletal assembly.

血小板对生理性刺激的反应介导血小板伤口部位的聚集对于止血是至关重要的。这个血小板反应和前列腺素I2的逆转也可能是对动脉粥样硬化的病理生理学很重要，血栓性静脉炎和中风本项目的长期目标是了解活化过程中血小板细胞骨架组装的调节（肌动蛋白聚合、肌球蛋白和肌动蛋白结合蛋白磷酸化和与肌动蛋白丝的相互作用），逆转血小板PGI 2升高激活细胞骨架组装 cAMP，以及这种细胞骨架的关系组装/拆卸到表面膜位点的表达介导活化、粘附和聚集。朝向为了达到这一目的，建议分离肌动蛋白结合蛋白，蛋白质，以确定其与肌动蛋白的相互作用是否被修改，其在活化过程中被蛋白激酶C原位磷酸化和cAMP依赖性激酶在逆转或抑制活化-细胞骨架组装。膜糖蛋白- 细胞骨架复合物已从PGI 2失活的血小板建议确定这些络合物是否是血小板活化所必需的，细胞骨架组装以及这种组装的破坏复合物是某些两亲性的化合物抑制血小板活化-细胞骨架组装。