Department of Pathology, Boston University School of Medicine, 670 Albany Street, Boston, MA 02118, USA.
Biochem Soc Trans. 2009 Dec;37(Pt 6):1189-92. doi: 10.1042/BST0371189.
Regulation of angiogenesis is often viewed as a balance between pro-angiogenic and anti-angiogenic factors, and when the balance shifts in favour of angiogenesis stimulators, an angiogenic switch turns on the normally inactive endothelial cells to grow new blood vessels. Recent studies have shown that PLCgamma1 (phospholipase Cgamma1), a major signalling substrate of VEGFR-2 (vascular endothelial growth factor receptor 2), undergoes c-Cbl-mediated ubiquitination. c-Cbl suppresses tyrosine phosphorylation of PLCgamma1 and with it VEGF (vascular endothelial growth factor)-induced endothelial cell proliferation and angiogenesis. Loss of c-Cbl in mice results in enhanced retinal neovascularization, VEGF- and tumour-induced angiogenesis. Notably, this observation suggests that c-Cbl-mediated ubiquitination pathway plays a central role in the 'angiogenic switch' employed by the VEGF system. The present article highlights the recent findings demonstrating a novel role for protein ubiquitination in angiogenesis and its potential in angiogenesis-based therapy.
血管生成的调节通常被视为促血管生成和抗血管生成因子之间的平衡，当平衡向血管生成刺激物倾斜时，血管生成开关会激活通常处于非活动状态的内皮细胞以生长新的血管。最近的研究表明，PLCγ1（磷脂酶 Cγ1）是 VEGFR-2（血管内皮生长因子受体 2）的主要信号底物，经历 c-Cbl 介导的泛素化。c-Cbl 抑制 PLCγ1 的酪氨酸磷酸化，从而抑制 VEGF（血管内皮生长因子）诱导的内皮细胞增殖和血管生成。c-Cbl 在小鼠中的缺失会导致视网膜新生血管形成增强、VEGF 和肿瘤诱导的血管生成。值得注意的是，这一观察结果表明，c-Cbl 介导的泛素化途径在 VEGF 系统所采用的“血管生成开关”中发挥着核心作用。本文重点介绍了最近的发现，这些发现证明了蛋白质泛素化在血管生成中的新作用及其在基于血管生成的治疗中的潜力。
