Mechanism of LSA Induced Outside-in Signal Transduction

描述：（研究者摘要）本提案的长期目标 目的是阐明细胞外基质介导的由外向内的信号转导机制。 血小板纤维蛋白原受体，整合素α IIb/β 3。阐明 人血小板的外部信号转导机制是重要的基础 research.这项研究很重要，不仅是因为 血小板在心血管疾病中的作用， 由外向内的信号转导是细胞生物学的核心， 将军深入了解由外向内信号的分子细节 血小板中的转导可能为设计一种 能够控制至少一些血小板行为的药剂 其有助于心血管疾病的发展和进展。的 该提案的长期目标将通过描述 一种独特的受体激活肽对血小板功能的影响。这 受体活化肽似乎通过结合 α IIb，从而引起纤维蛋白原受体的构象变化 其启动血小板活化信号转导级联， 最终导致“不可逆的”血小板聚集。中描述的实验 这个提议旨在揭示受体的结合如何激活 肽与受体的相互作用引发由外向内的信号转导。但愿， 这些实验将揭示受体内亚基的类型， 启动由外向内信号转导的受体间相互作用 血小板的反应，并确定信号的主要成分 用于传播这种由外向内信号传导的转导途径。

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.