Mechanism of LSA Induced Outside-in Signal Transduction

描述：(研究人员摘要)这项提议的长期目标 目的是阐明细胞外向内信号转导的机制。 血小板纤维蛋白原受体，整合素αIIb/β3。澄清： 人血小板外源信号转导机制是重要的基础 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作用也是因为对其机制的洞察 外向内信号转导在细胞生物学中具有重要意义 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。这个 这项提案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小板功能的影响。这 受体激活肽似乎通过与受体结合引起血小板聚集 从而引起纤维蛋白原受体的构象变化 它启动了一系列的血小板激活信号转导 最终导致“不可逆”的血小板聚集。中描述的实验 这一建议旨在揭示结合受体如何激活 受体上的多肽引发了由外向内的信号转导。但愿能去, 这些实验将揭示受体内亚单位的类型或 启动自外向内信号转导的受体间相互作用 对血小板的反应，并确定信号的主要成分 用来传播这种由外而内信号的转导通路。

DESCRIPTION: (Investigator's abstract) The long term objective of this 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-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 elicits outside-in signal transduction. 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 and identify the major components of the signal transduction pathway used to propagate this outside-in signaling.