MECHANISM OF PLATELET ACTIVATION BY THE PEPTIDE LSARLAF

描述：(研究人员摘要)该计划的长期目标 这里描述的研究是为了阐明外向内信号的机制 血小板纤维蛋白原受体糖蛋白介导的信号转导 IIb/IIIa复合体(也称为整合素AlphaIIb/Beta3)。澄清 人血小板外源信号转导机制的研究 重要的基础研究。这项研究之所以重要，不仅是因为 血小板在心血管疾病中的核心作用也是因为 对外向内信号转导机制的洞察具有重要意义 对一般细胞生物学的重要性。洞察分子 血小板内由外向内信号转导的细节可能提供 设计一种药剂的基本原理能够至少控制 一些有助于发育和发育的血小板行为 心血管疾病的进展。 这项提议的长期目标将通过以下方式实现 一种独特的受体激活肽对血管内皮细胞的作用 血小板功能。这种受体激活肽似乎能引起 通过与GPIIb结合从而引起血小板聚集 启动血小板的纤维蛋白原受体的构象变化 最终导致“不可逆转”的激活信号转导级联 血小板聚集。本提案中描述的实验包括 旨在揭示受体激活肽如何结合到 受体使之前不活跃的受体能够与 纤维蛋白原，并确定纤维蛋白原结合是否必要 由受体进行的后续信号转导或如果后续信号 在没有纤维蛋白原的受体交联的情况下，信号转导可以发生。 或者是配体。希望这些实验将揭示出 受体内亚单位或受体间相互作用启动 血小板内由外向内的信号转导反应。

DESCRIPTION: (Investigator's abstract) The long term objective of the research described here is to elucidate the mechanism of outside-in signal transduction mediated by the platelet fibrinogen receptor, the glycoprotein IIb/IIIa complex (also known as the integrin alphaIIb/beta3). Elucidation of the mechanism of outside-signal transduction in human platelets is important basic research. This research is important not only because of the central role of platelets in cardiovascular disease but also because insight into the mechanism of outside-in signal transduction is of central importance to cell biology in general. Gaining insight into the molecular details of outside-in signal transduction in platelets may provide a rationale for the design of a pharmaceutical agent able to control at least some of the platelet behavior which contributes to development and progression of cardiovascular disease. The long term objective of this proposal will be accomplished by characterizing the effects of a unique receptor activating peptide on platelet function. This receptor activating peptide appears to cause platelet aggregation by binding to GPIIb and thereby eliciting a conformation change in the fibrinogen receptor which initiates a platelet activation signal transduction cascade that culminates in "irreversible" platelet aggregation. The experiments described in this proposal are designed to reveal how binding of the receptor activating peptide to the receptor enables the previously inactive receptor to be able to bind fibrinogen and to determine if fibrinogen binding is necessary for subsequent signal transduction by the receptor or if subsequent signal transduction can occur in the absence of receptor crosslinking by fibrinogen or ligands. Hopefully, these experiments will reveal the type of intra-receptor subunit or inter-receptor interactions which initiate the outside-in signal transduction response in platelets.