PLATELET CYTOSKELETAL ASSEMBLY & FUNCTION

血小板对介导血小板的生理刺激的反应 伤口处的聚集是止血的关键。这个血小板 前列腺素I2的反应和逆转也可能是 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。 该项目的长期目标是了解 活化过程中对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细丝的相互作用)，逆转 PGI2升高血小板激活细胞骨架的组装 CAMP，以及这种细胞骨架之间的关系 组装/拆卸对表膜位点表达的影响 调节激活、黏附和聚集。朝向 为了达到这一目的，建议分离肌动蛋白结合 以确定其与肌动蛋白的相互作用是否被 其在激活过程中被蛋白激酶C原位磷酸化 并通过cAMP依赖的激酶在逆转或抑制 激活--细胞骨架组装。膜糖蛋白- 从灭活的PGI2中分离出细胞骨架复合体 血小板。有人建议确定这些复合体是否 是血小板活化所必需的调节前体 细胞骨架组装和这种破坏是否 络合物是某些两亲性的机理 化合物抑制血小板激活--细胞骨架组装。

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.