RhoB controls endothelial cell morphogenesis in part via negative regulation of RhoA

Angiogenesis is a normal process involved in development, reproduction, and wound healing, as new blood vessels are formed from the pre-existing vasculature. Despite being a beneficial event under certain circumstances, angiogenesis is also a major contributing factor to several diseases including, rheumatoid arthritis, cancer, and ocular diseases such as diabetic retinopathy (reviewed in [1-3]). Angiogenesis is a multi-step event that requires growth factor stimulation of endothelial cells, resulting in cellular proliferation, migration, tube formation, and finally stabilization of the new vessels. As angiogenesis only initiates following angiogenic growth factor stimulation, many strategies that target primary angiogenic factors, such as vascular endothelial cell growth factor (VEGF) or its angiogenic receptor (VEGFR) have been developed and are at various stages of clinical testing. Although these types of anti-angiogenic therapies have shown some ability to control disease in certain settings, recent studies have highlighted an increased risk of severe side effects with the widely used anti-angiogenic, Bevacizumab (reviewed in [4-6]). For reasons such as this, the discovery of novel mechanisms controlling angiogenesis is necessary so that new therapeutic targets can be identified.RhoB is a member of the Ras superfamily of GTPases, which includes proteins such as Rac1, Cdc42, RhoA, and RhoC. Rho family proteins (with the exception of RhoE) are GTPases that function by cycling through a GTP-bound activated state and a GDP-bound inactive state. Regulation of these states is achieved through GTPase-activating proteins (GAPs), guanine nucleotide exchange factors (GEFs), and guanine nucleotide dissociation inhibitors (GDIs) [7]. RhoB shares ~80% homology with its closely related family members RhoA and RhoC, however its subcellular localization was found to be very different, with almost exclusive localization to the cytosolic face of early endosomes and pre-lysosomal