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: 2895807
• 负责人: DAVID B DONNER
• 金额: $ 23.03万
• 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/2895807
• 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（改编自研究者摘要）：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）。 VEGF 作用的第一步是与两个中的任何一个结合 受体酪氨酸激酶 Flk-1 和 Flt-1。 这些受体的作用 介导细胞对 VEGF 的反应尚未明确定义，也未明确 促进任一受体活性的信号通路。 使用 特异性靶向和降解 Flk-1 的核酶/反义结构 Flt-1，他们将分离出其中一种或另一种 VEGF 的内皮细胞 受体已被敲除。 此类单元格将用于定义 Flk-1 和 Flt-1 介导的反应。 从转导途径中 他们发现磷脂酰肌醇与 VEGF 作用相关 3-激酶和丝裂原激活蛋白激酶尤其重要。 这些系统在促进 VEGF 诱导的多种反应中的作用 将被定义。 最后，他们发现蛋白质酪氨酸 磷酸酶可以正向和负向调节 VEGF 的作用。 角色 这些磷酸酶，特别是两种 - SYP 和 LAR，在调节 VEGF 中的作用 将定义对 VEGF 的信号传导和细胞反应。