VEGFR-1 and VEGFR-2 in angiogenesis

描述(申请人提供)：血管生成是一个基本的过程 仅在正常发育中，但在肿瘤生长等病理条件下 和转移。新的和改进的预防血管生成的方法需要 了解调节血管生成的机制。血管 血管内皮细胞生长因子及其受体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激活刺激血管生成，而VEGFR-1 激活似乎通过刺激血管生成来发挥双重功能 或抑制血管生成。因此，理解分子机制 在这些截然不同的影响下，是发展 以抑制血管生成为目标的针对性治疗干预。 这项提案的总体目标是调查 VEGFRs被激活，并利用这些差异来抑制血管生成。 这一建议集中在配体结合导致 血管内皮生长因子受体的激活，信号转导的一个基本问题和 血管生成。一旦我们确定了血管内皮生长因子受体 使血管新生信号转导减弱成为可能。 通过开发针对血管生成的有针对性的治疗干预来传递 压制

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