MECHANISM OF PLATELET ACTIVATION BY THE PEPTIDE LSARLAF

肽 LSARLAF 激活血小板的机制

• 批准号: 2613016
• 负责人: T. KENT GARTNER
• 金额: $ 9.8万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2613016
• 关键词: binding proteins; biological signal transduction; cell adhesion; conformation; crosslink; fibrinogen receptors; human tissue; integrins; peptides; phosphorylation; platelet activation; platelet aggregation; protein sequence; protein structure function; receptor binding; secretion

DESCRIPTION: The long term objective of this Academic Research Enhancement Award proposal is to elucidate the mechanism of outside-in signal transduction mediated by the platelet fibrinogen receptor, the integrin alphaIIb-beta3. Elucidation of the mechanism of outside- in 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 alphaIIb 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.

描述：这项学术研究强化的长期目标 奖励方案是为了阐明由外而内的信号机制 血小板纤维蛋白原受体整合素介导的信号转导 字母IIb-β3。阐明自外向内信号产生的机制 人血小板转导是重要的基础研究。这项研究 之所以重要，不仅是因为血小板在 心血管疾病，也是因为对其发病机制的洞察 由外而内的信号转导对细胞生物学具有重要意义。 将军。深入了解自外向内信号的分子细节 血小板中的转导可能为设计一种 能够控制至少部分血小板行为的药剂 这有助于心血管疾病的发展和进展。 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AlphaIIb结合而引起的血小板聚集 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。