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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pfizenmaier, Klaus Hausser, Angelika Olson, Eric N. Jin, Zheng-gen Mckinsey, Timothy A. Wang, Weiye Jhun, Bong Sook Ha, Chang Hoon Wong, Chelsea |
| Description | Author Affiliation: Ha CH ( Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14586, USA.) |
| Abstract | Vascular endothelial growth factor (VEGF) is essential for normal and pathological angiogenesis. However, the signaling pathways linked to gene regulation in VEGF-induced angiogenesis are not fully understood. Here we demonstrate a critical role of protein kinase D (PKD) and histone deacetylase 5 (HDAC5) in VEGF-induced gene expression and angiogenesis. We found that VEGF stimulated HDAC5 phosphorylation and nuclear export in endothelial cells through a VEGF receptor 2-phospholipase Cgamma-protein kinase C-PKD-dependent pathway. We further showed that the PKD-HDAC5 pathway mediated myocyte enhancer factor-2 transcriptional activation and a specific subset of gene expression in response to VEGF, including NR4A1, an orphan nuclear receptor involved in angiogenesis. Specifically, inhibition of PKD by overexpression of the PKD kinase-negative mutant prevents VEGF-induced HDAC5 phosphorylation and nuclear export as well as NR4A1 induction. Moreover, a mutant of HDAC5 specifically deficient in PKD-dependent phosphorylation inhibited VEGF-mediated NR4A1 expression, endothelial cell migration, and in vitro angiogenesis. These findings suggest that the PKD-HDAC5 pathway plays an important role in VEGF regulation of gene transcription and angiogenesis. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 21 |
| Volume Number | 283 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2008-05-23 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Gene Expression Regulation Drug Effects Histone Deacetylases Metabolism Neovascularization, Physiologic Protein Kinase C Vascular Endothelial Growth Factor A Pharmacology Active Transport, Cell Nucleus Animals Cell Movement Cells, Cultured Endothelial Cells Cytology Enzymology Genetics Phospholipase C Gamma Phosphorylation Phosphoserine Signal Transduction Transcription Factors Transcriptional Activation Vascular Endothelial Growth Factor Receptor-2 Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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