Raf comprises a family of three kinases, A-Raf, B-Raf and Raf-1—which are key regulators of the MEK-MAPK/ERK cascade. The MAP Kinase pathway is an important signaling mechanism regulating cellular functions such as growth, transformation, and apoptosis, but the exact role of Raf kinases in endothelial cell survival has been unclear. In the July 4 Science, Alireza Alavi and colleagues at the Scripps Research Institute show that Raf-1 is a pivotal regulator of endothelial cell survival during angiogenesis (Science, 301:94-96, July 4, 2003).

Alavi et al. used human endothelial cells and chick embryo vasculature exposed to individual growth factors. They observed that that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) differentially activate Raf, resulting in protection from distinct pathways of apoptosis. bFGF activated Raf-1 via p21-activated protein kinase–1 (PAK-1) phosphorylation of serines 338 and 339, resulting endothelial cell protection from the intrinsic (stress) pathway of apoptosis....

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