Journal
SCIENCE
Volume 301, Issue 5629, Pages 94-96Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1082015
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Funding
- NCI NIH HHS [CA50286, P01 CA78045, CA45726, CA75924] Funding Source: Medline
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Raf kinases have been linked to endothelial cell survival. Here, we show that basic fibroblast growth factor ( bFGF) and vascular endothelial growth factor ( VEGF) differentially activate Raf, resulting in protection from distinct pathways of apoptosis in human endothelial cells and chick embryo vasculature. bFGF activated Raf-1 via p21-activated protein kinase-1 (PAK-1) phosphorylation of serines 338 and 339, resulting in Raf-1 mitochondrial translocation and endothelial cell protection from the intrinsic pathway of apoptosis, independent of the mitogen-activated protein kinase kinase-1 (MEK1). In contrast, VEGF activated Raf-1 via Src kinase, leading to phosphorylation of tyrosines 340 and 341 and MEK1-dependent protection from extrinsic-mediated apoptosis. These findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis.
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