Abstract
Src kinase activity was found to protect endothelial cells from apoptosis during vascular endothelial growth factor (VEGF)-, but not basic fibroblast growth factor (bFGF)-, mediated angiogenesis in chick embryos and mice. In fact, retroviral targeting of kinase-deleted Src to tumor-associated blood vessels suppressed angiogenesis and the growth of a VEGF-producing tumor. Although mice lacking individual Src family kinases (SFKs) showed normal angiogenesis, mice deficient in pp60c-src or pp62c-yes showed no VEGF-induced vascular permeability (VP), yet fyn-/- mice displayed normal VP. In contrast, inflammation-mediated VP appeared normal in Src-deficient mice. Therefore, VEGF-, but not bFGF-, mediated angiogenesis requires SFK activity in general, whereas the VP activity of VEGF specifically depends on the SFKs, Src, or Yes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology
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Capillary Permeability / drug effects
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Capillary Permeability / physiology*
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Chick Embryo
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Endothelial Growth Factors / pharmacology
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Endothelial Growth Factors / physiology*
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Endothelium, Vascular / pathology*
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Endothelium, Vascular / physiology*
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Fibroblast Growth Factor 2 / pharmacology
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Lymphokines / pharmacology
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Lymphokines / physiology*
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Mice
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Mice, Knockout
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Neovascularization, Pathologic*
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Neovascularization, Physiologic*
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-yes
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Proto-Oncogene Proteins pp60(c-src) / physiology
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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src-Family Kinases / physiology*
Substances
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Endothelial Growth Factors
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Lymphokines
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Proto-Oncogene Proteins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Fibroblast Growth Factor 2
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Proto-Oncogene Proteins c-yes
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Proto-Oncogene Proteins pp60(c-src)
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Yes1 protein, mouse
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src-Family Kinases