Plcg1 integration of Vegf receptor signaling

描述（由申请人提供）：了解血管内皮生长因子（Vegf）信号分子的功能和调控及其在血管发育中的作用已经变得越来越重要，因为驱动这一过程的机制与血管病理所使用的机制相同。更好地了解这一发育过程将是开发治疗和诊断许多血管疾病（如心脏病、癌症和糖尿病）的关键。利用柔韧的脊椎动物遗传系统，如斑马鱼，使血管发育的研究既可行又有效。在这个建议中，我们挑选出磷脂酶C γ 1 （plcg1）作为Vegf受体（Vegfr）信号的唯一整合者。通过使用plcg1 SH2结构域的突变形式和plcg1激活位点的突变体进行一系列的结构功能分析，我们将确定这些成分对血管发育的必要性，并确定plcg1和Vegfrs之间促进这一过程所需的关键相互作用。

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.