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， 仅在正常发育中，但在病理条件下， 和转移。用于预防血管生成的新的和改进的方法需要一种 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-1和 VEGFR-2/Flk-1/KDR）被认为是肿瘤诱导的细胞凋亡的主要调节因子。 血管生成VEGFR-2的激活刺激血管生成，而VEGFR- 1 激活似乎通过刺激血管生成 或抑制血管生成。因此，了解分子机制 这些截然不同的影响是发展的基础， 针对血管生成抑制的靶向治疗干预。 本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。 这一建议的重点是配体结合的机制，在这种情况下， VEGF受体的激活，这是信号转导中的基本问题， 血管生成一旦我们确定了VEGF受体的作用机制， 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靶向治疗干预措施， 抑制

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