2008
DOI: 10.1073/pnas.0802857105
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Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7

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. … Show more

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Cited by 229 publications
(216 citation statements)
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“…Both Egr3 and Nurr77 are required for effective VEGF-mediated migration and tube formation in HUVECs, suggesting that PKD may regulate angiogenic responses in part by mediating transcription of these genes (10,31). HDAC7 also regulates Nurr77 transcription via MEF2, and another gene, RCAN2, which stimulates angiogenesis via the calcineurin-NFAT pathway (29,32). As with HDAC5, HDAC7 phosphorylation and subsequent nuclear export were stimulated by VEGF and mediated by PKD1 (29).…”
Section: Pkd Function In Endothelial Cellsmentioning
confidence: 97%
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“…Both Egr3 and Nurr77 are required for effective VEGF-mediated migration and tube formation in HUVECs, suggesting that PKD may regulate angiogenic responses in part by mediating transcription of these genes (10,31). HDAC7 also regulates Nurr77 transcription via MEF2, and another gene, RCAN2, which stimulates angiogenesis via the calcineurin-NFAT pathway (29,32). As with HDAC5, HDAC7 phosphorylation and subsequent nuclear export were stimulated by VEGF and mediated by PKD1 (29).…”
Section: Pkd Function In Endothelial Cellsmentioning
confidence: 97%
“…HDAC7 also regulates Nurr77 transcription via MEF2, and another gene, RCAN2, which stimulates angiogenesis via the calcineurin-NFAT pathway (29,32). As with HDAC5, HDAC7 phosphorylation and subsequent nuclear export were stimulated by VEGF and mediated by PKD1 (29). It is possible that other genes are transcriptionally regulated by PKD and these remain to be determined.…”
Section: Pkd Function In Endothelial Cellsmentioning
confidence: 99%
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“…Migration of kidney pericytes and kidney MVECs was assessed using a scratch wound assay as described 5,37 with some modifications.…”
Section: Migration Assaysmentioning
confidence: 99%
“…The signal transduction pathways that are activated in different cell types in response to VEGF are well established (Cross et al, 2003;Wang et al, 2008). However, relatively little is known about the involvement of distinct phosphoinositide 3-kinase (PI3K) catalytic subunits and protein kinase C (PKC) isoforms in VEGF action (Hamada et al, 2005;Gliki et al, 2002;Gerber et al, 1998).…”
Section: Introductionmentioning
confidence: 99%