Plcg1 integration of Vegf receptor signaling

Plcg1 整合 Vegf 受体信号传导

• 批准号: 7129023
• 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/7129023
• 关键词: Arteries; Automobile Driving; Blood Vessels; Complement; Data; Defect; Development; Developmental Process; Diabetes Mellitus; Diagnosis; Disruption; Embryo; Genes; Genetic; Heart Diseases; Homologous Gene; Malignant Neoplasms; Molecular; Mutate; Organism; PLC gamma1; Pathology; Pattern; Phenotype; Process; Receptor Signaling; Regulation; Role; Series; Signal Transduction; Site; Structure; System; Transcript; Vascular Diseases; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factor Receptor-3; Vascular Endothelial Growth Factors; Vertebrates; Zebrafish; in vivo; mutant; receptor; src Homology Region 2 Domain; therapy development

spaceprovided) Understanding the function and regulation of molecules involved in Vascular endothelial growth factor (Vegt) 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 (plcgl) as the sole integrator of signals derived from Vegf receptors (Vegfr). Through a series of structure function analysis using mutated forms of plcgl SH2 domains and mutants in plcgl activation sites, we will determine the necessity of each of these components for blood vessel development, as well as identify key interactions between plcgl and Vegfrs that are needed to promote this process.

提供空间) 了解血管内皮生长因子(VETT)相关分子的功能和调控 信号及其在血管发育中的作用变得越来越重要，因为 推动这一过程的机制与血管病理学使用的机制相同。更好的 对这一发育过程的理解将是发展治疗和诊断的关键。 许多血管疾病，如心脏病、癌症和糖尿病。使用一种柔软的脊椎动物 斑马鱼等遗传系统使血管发育的研究既可行又 效率很高。在这个建议中，我们挑选出磷脂酶C-γ1(Plcgl)作为信号的唯一积分器 来源于血管内皮生长因子受体(VEGFR)。通过使用突变形式的一系列结构功能分析 Plcgl sh2结构域和突变体，我们将确定每一个的必要性。 用于血管发育的组件，以及确定plcgl和Vegfrs之间的关键交互作用 是推动这一进程所必需的。