MECHANISM OF PLATELET ACTIVATION BY THE PEPTIDE LSARLAF

描述：（研究者摘要） 本文所描述的研究是为了阐明由外向内信号的机制 由血小板纤维蛋白原受体，糖蛋白 IIb/IIIa复合物（也称为整合素α IIb/β 3）。 阐发 人血小板外部信号转导的机制是 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， 深入了解由外向内的信号转导机制是 对细胞生物学的重要性。 深入了解 血小板中由外向内的信号转导的细节可以提供 设计能够控制至少 一些血小板的行为，这有助于发展， 心血管疾病的进展。 本建议的长远目标将通过以下方式实现： 表征一种独特的受体活化肽对 血小板功能 这种受体激活肽似乎引起 血小板通过与GPIIb结合而聚集，从而引发血小板聚集。 纤维蛋白原受体的构象变化， 激活信号转导级联，最终导致“不可逆” 血小板聚集 本提案中描述的实验是 旨在揭示受体激活肽如何与 受体使以前无活性的受体能够结合 纤维蛋白原，并确定纤维蛋白原结合是否是必要的， 受体的后续信号转导，或者如果后续信号 在没有纤维蛋白原引起的受体交联的情况下 或配体。 希望这些实验能揭示 受体内亚基或受体间相互作用， 血小板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.