VEGFR-1 and VEGFR-2 in angiogenesis

描述（由申请人提供）：血管生成是一个重要的过程，而不是 仅在正常发育中，但在肿瘤生长等病理条件下 和转移。预防血管生成的新的和改进的方法需要 了解调节血管生成的机制。血管 内皮生长因子 (VEGF) 及其受体 (VEGFR-lIFlt-l 和 VEGFR-2/Flk-1/KDR)被认为是肿瘤诱导的主要调节因子 血管生成。 VEGFR-2 的激活刺激血管生成，而 VEGFR-1 的激活 激活似乎通过刺激血管生成发挥双重功能 或抑制血管生成。因此，了解分子机制 这些显着不同的影响的背后对于发展至关重要 旨在抑制血管生成的有针对性的治疗干预措施。 该提案的总体目标是研究机制 VEGFR 被激活并利用这些差异来抑制血管生成。 该提案重点关注配体结合导致 VEGF 受体的激活，信号转导的一个基本问题 血管生成。一旦我们确定了 VEGF 受体的作用机制 参与将有可能减弱血管生成信号转导 通过开发针对血管生成的有针对性的治疗干预措施来接力 镇压

DESCRIPTION (Provided by applicant): Angiogenesis is an essential process not only in normal development, but in pathological conditions such as tumor growth and metastasis. New and improved methods for preventing angiogenesis require an understanding of the mechanisms that regulate angiogenesis. Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-lIFlt-l and VEGFR-2/Flk-1/KDR) are considered to be primary regulators of tumor-induced angiogenesis. Activation of VEGFR-2 stimulates angiogenesis, while VEGFR- 1 activation appears to play a dual function by either stimulating angiogenesis or suppressing angiogenesis. Therefore, understanding the molecular mechanisms underlying these strikingly different effects is essential for development of targeted therapeutic interventions aimed at angiogenesis suppression. The overall goal of this proposal is to investigate the mechanism by which VEGFRS are activated and to exploit these differences to suppress angiogenesis. This proposal focuses on the mechanism by which ligand binding results in the activation of VEGF receptors, a fundamental issue in signal transduction and angiogenesis. Once we determine the mechanism by which VEGF receptors are engaged it will be possible to attenuate the angiogenic signal transduction relay by developing targeted therapeutic interventions aimed at angiogenesis suppression