ArticleThe Biochemical journal2001
Vascular endothelial growth factor-induced prostacyclin production is mediated by a protein kinase C (PKC)-dependent activation of extracellular signal-regulated protein kinases 1 and 2 involving PKC-delta and by mobilization of intracellular Ca2+.
Article in The Biochemical journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 97 citations in OpenAlex.
- Ischemic Preconditioning Improves Microvascular Endothelial Function in Remote Vasculature by Enhanced Prostacyclin Production.Journal of the American Heart Association · 2020Trial
- Loss of diacylglycerol kinase ε causes thrombotic microangiopathy by impairing endothelial VEGFA signaling.JCI insight · 2021Article
- Molecular Bases of VEGFR-2-Mediated Physiological Function and Pathological Role.Frontiers in cell and developmental biology · 2020Review
- Endothelial loss of Fzd5 stimulates PKC/Ets1-mediated transcription of Angpt2 and Flt1.Angiogenesis · 2018Article
- Upregulation of microRNA-205 suppresses vascular endothelial growth factor expression-mediated PI3K/Akt signaling transduction in human keloid fibroblasts.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Vascular Endothelial Growth Factor (VEGF) Promotes Assembly of the p130Cas Interactome to Drive Endothelial Chemotactic Signaling and Angiogenesis.Molecular & cellular proteomics : MCP · 2017Article
- The anticoagulant effect of PGI2S and tPA in transgenic umbilical vein endothelial cells is linked to up-regulation of PKA and PKC.International journal of molecular sciences · 2014Article
- Hypoxia induces permeability and giant cell responses of Andes virus-infected pulmonary endothelial cells by activating the mTOR-S6K signaling pathway.Journal of virology · 2013Article
- Regulation of endothelial MAPK/ERK signalling and capillary morphogenesis by low-amplitude electric field.Journal of the Royal Society, Interface · 2013Article
- Angiopoietin-1 and vascular endothelial growth factor regulation of leukocyte adhesion to endothelial cells: role of nuclear receptor-77.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation.Molecular biology of the cell · 2011Article
- Angiogenic functions of voltage-gated Na+ Channels in human endothelial cells: modulation of vascular endothelial growth factor (VEGF) signaling.The Journal of biological chemistry · 2011Article
- Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells.The Biochemical journal · 2010Article
- Sprouty2 interacts with protein kinase C delta and disrupts phosphorylation of protein kinase D1.The Journal of biological chemistry · 2009Article
- The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis.Oncogene · 2008Article
- Cartilage-selective genes identified in genome-scale analysis of non-cartilage and cartilage gene expression.BMC genomics · 2007Article
- The role of VEGF receptors in angiogenesis; complex partnerships.Cellular and molecular life sciences : CMLS · 2006Review
- Lysophosphatidylcholine and 7-oxocholesterol modulate Ca2+ signals and inhibit the phosphorylation of endothelial NO synthase and cytosolic phospholipase A2.The Biochemical journal · 2004Article
- Fatty acid mobilized by the vascular endothelial growth factor in human endothelial cells.Lipids · 2002Article
- Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells.The Biochemical journal · 2001Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We reported previously that vascular endothelial growth factor (VEGF) stimulates prostacyclin (PGI(2)) production via activation of the extracellular signal-regulated kinase (ERK) cascade. In this paper, we examined the role of protein kinase C (PKC) in this pathway. VEGF-induced PGI(2) generation and arachidonic acid release in human umbilical vein endothelial cells were inhibited by the PKC inhibitors GF109203X and calphostin C. VEGF increased PKC activity and immunoreactivity of the PKCdelta, alpha and epsilon isoforms in particulate fractions of cells. PKC inhibitors blocked VEGF-induced activation of ERK, MEK (mitogen-activated protein kinase kinase) and the cytosolic phospholipase A(2), but had little effect on ERK activation induced by basic fibroblast growth factor. GF109203X, calphostin C and the PKCdelta-selective inhibitor, rottlerin, did not inhibit activation of the KDR receptor for VEGF. Inhibition of Ca(2+) fluxes using BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)] blocked VEGF-induced PGI(2) production but did not inhibit ERK activation. Neither activation nor inhibition of the NO/cGMP pathway had any effect on VEGF induction of ERK activity and PGI(2) synthesis. Wortmannin partially inhibited VEGF stimulation of PGI(2) production, but did not inhibit VEGF-induced ERK activity. VEGF-induced ERK activation and PGI(2) production were blocked by rottlerin, and VEGF increased association of PKCdelta with Raf-1, the upstream activator of MEK. The PKC-selective inhibitor Go6976 did not inhibit ERK activation and had only a partial effect on PGI(2) production. These findings indicate that activation of PKC plays a crucial role in VEGF signalling via the ERK cascade leading to PGI(2) synthesis and suggest that the PKCdelta isoform may be a key mediator of VEGF-induced activation of the ERK pathway via increased association with Raf-1.
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