Abstract
VEGF has been shown to regulate endothelial cell (EC) proliferation and migration. However, the nuclear mediators of the actions of VEGF in ECs have not been fully defined. We show that VEGF induces the phosphorylation of three conserved serine residues in histone deacetylase 7 (HDAC7) via protein kinase D, which promotes nuclear export of HDAC7 and activation of VEGF-responsive genes in ECs. Expression of a signal-resistant HDAC7 mutant protein in ECs inhibits proliferation and migration in response to VEGF. These results demonstrate that phosphorylation of HDAC7 serves as a molecular switch to mediate VEGF signaling and endothelial function.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Cell Line
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Cell Movement*
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Cell Proliferation*
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Endothelial Cells / drug effects
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Endothelial Cells / enzymology
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Endothelial Cells / physiology*
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Gene Expression Regulation
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Humans
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Intercellular Signaling Peptides and Proteins / pharmacology
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Mutation
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Neovascularization, Physiologic* / drug effects
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Neovascularization, Physiologic* / genetics
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Phosphorylation
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Protein Kinase C / metabolism
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Serine / genetics
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Serine / metabolism
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Signal Transduction
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Vascular Endothelial Growth Factor A / pharmacology
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Vascular Endothelial Growth Factor A / physiology*
Substances
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Intercellular Signaling Peptides and Proteins
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Vascular Endothelial Growth Factor A
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Serine
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protein kinase D
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Protein Kinase C
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HDAC7 protein, human
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Histone Deacetylases