Plcg1 integration of Vegf receptor signaling

Plcg1 整合 Vegf 受体信号传导

• 批准号: 6985540
• 负责人: Jacques Alphonse Villefranc
• 金额: $ 2.86万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-30 至 2009-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6985540
• 关键词: active sites; angiogenesis; biological signal transduction; enzyme mechanism; gene mutation; growth factor receptors; phospholipase C; phosphorylation; predoctoral investigator; protein protein interaction; protein structure function; vascular endothelial growth factors; zebrafish

DESCRIPTION (provided by applicant): Understanding the function and regulation of molecules involved in Vascular endothelial growth factor (Vegf) signaling and it's role in blood vessel development have become of increasing significance since the mechanisms that drive this process are the same as those used by vascular pathologies. A better understanding of this developmental process will be key in the development of therapies and diagnoses of many vascular disorders such as heart disease, cancer, and diabetes. The use of a pliable vertebrate genetic system such as the Zebrafish makes the study of blood vessel development both feasible and efficient. In this proposal we single out phospholipase C gamma 1 (plcg1) as the sole integrator of signals derived from Vegf receptors (Vegfr). Through a series of structure function analysis using mutated forms of plcg1 SH2 domains and mutants in plcg1 activation sites, we will determine the necessity of each of these components for blood vessel development, as well as identify key interactions between plcg1 and Vegfrs that are needed to promote this process.

描述（由申请人提供）：了解参与血管内皮生长因子（VEGF）信号传导的分子的功能和调节及其在血管发育中的作用已变得越来越重要，因为驱动该过程的机制与血管病理学所使用的机制相同。更好地了解这一发展过程将是发展治疗和诊断许多血管疾病，如心脏病，癌症和糖尿病的关键。使用像斑马鱼这样柔韧的脊椎动物遗传系统使得血管发育的研究既可行又有效。在这个提议中，我们挑选出磷脂酶C γ 1（plcg1）作为来自VEGF受体（Vegfr）的信号的唯一积分器。通过一系列的结构功能分析，使用突变形式的plcg1 SH2结构域和突变体的plcg1激活位点，我们将确定这些组件中的每一个的必要性血管发展，以及确定关键的plcg1和Vegfrs之间的相互作用，需要促进这一进程。