VASCULAR ENDOTHELIAL CELL GROWTH FACTOR IN PATHOLOGY

病理学中的血管内皮细胞生长因子

• 批准号: 2733318
• 负责人: DAVID B DONNER
• 金额: $ 22.36万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733318
• 关键词: angiogenesis; biological signal transduction; enzyme mechanism; mitogen activated protein kinase; pathologic process; phosphatidylinositol 3 kinase; protein metabolism; protein tyrosine kinase; protein tyrosine phosphatase; tissue /cell culture; vascular endothelial growth factors

DESCRIPTION (Adapted from Investigator's Abstract): Vascular endothelial cell growth factor (VEGF) is a mitogen that promotes angiogenesis associated with physiological and pathological processes (cancer, rheumatoid arthritis, retinopathies). The first step in VEGF action is binding to either of two receptor tyrosine kinases, Flk-1 and Flt-1. The roles of these receptors in mediating cellular responses to VEGF have not been well defined nor have the signaling pathways that promote the activities of either receptor. Using ribozyme/antisense constructs that specifically target and degrade Flk-1 and Flt-1, they will isolate endothelial cells in which one or the other VEGF receptor has been knocked out. Such cells will be used to define the responses mediated by Flk-1 and Flt-1. From among the transduction pathways associated with VEGF action, they have found that phosphatidylinositol 3-kinase and mitogen activated protein kinases are especially important. The role of these systems in promoting diverse responses induced by VEGF will be defined. Finally, they have found that protein tyrosine phosphatases can positively and negatively regulate VEGF action. The role of such phosphatases, two in particular- SYP and LAR, in modulating VEGF signaling and cellular responses to VEGF will be defined.

描述(摘自《调查者摘要》)：血管内皮细胞 细胞生长因子(VEGF)是一种促进血管生成的有丝分裂原 与生理和病理过程(癌症、类风湿性关节炎、 视网膜病变)。血管内皮生长因子作用的第一步是绑定到两个中的任何一个 受体酪氨酸激酶、Flk-1和Flt-1。这些受体在细胞周期中的作用 介导细胞对血管内皮生长因子的反应还没有很好的定义，也没有 促进任一受体活性的信号通路。vbl.使用 特异性靶向并降解Flk-1和Flk-1的核酶/反义结构 Flt-1，他们将分离内皮细胞，其中一个或另一个血管内皮生长因子 感受器被破坏了。此类单元格将用于定义 Flk-1和Flt-1介导的应答。从这些转导途径中 与血管内皮生长因子的作用有关，他们发现磷脂酰肌醇 3-激酶和丝裂原激活的蛋白激酶尤其重要。 这些系统在促进血管内皮生长因子诱导的不同反应中的作用 将会被定义。最后，他们发现蛋白质酪氨酸 磷酸酶对血管内皮细胞生长因子的作用有正向和负向调节作用。角色 在这类磷酸酶中，有两种特别是--SYP和LAR--调节血管内皮生长因子 将定义对血管内皮细胞生长因子的信号和细胞反应。