VASCULAR ENDOTHELIAL CELL GROWTH FACTOR IN PATHOLOGY

描述（改编自研究者摘要）：血管内皮 细胞生长因子（VEGF）是一种促有丝分裂原， 具有生理和病理过程（癌症，类风湿性关节炎， 视网膜病变）。 VEGF作用的第一步是结合两种 受体酪氨酸激酶，Flk-1和Flt-1。 这些受体在 介导对VEGF的细胞应答还没有被很好地定义， 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/反义构建体， Flt-1，他们将分离内皮细胞，其中一个或另一个VEGF 受体被敲除。 这些单元格将用于定义 由Flk-1和Flt-1介导的应答。 从传导途径中 与VEGF作用相关，他们发现磷脂酰肌醇 3-激酶和促分裂原活化蛋白激酶是特别重要的。 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，他们发现蛋白酪氨酸 磷酸酶可以正向和负向调节VEGF的作用。 的作用 这类磷酸酶，特别是两种- SYP和LAR，在调节VEGF 将定义对VEGF的信号传导和细胞应答。

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.