Vascular Endothelial Growth Factor KDR Receptor Signaling Potentiates Tumor Necrosis Factor-induced Tissue Factor Expression in Endothelial Cells
| Autor: | Thomas F. Zioncheck, Ben-Quan Shen, Karen M. Cortopassi, Lisa A. Damico, David Y. Lee |
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| Rok vydání: | 2001 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Endothelial Growth Factors Biochemistry Thromboplastin chemistry.chemical_compound Tissue factor Proto-Oncogene Proteins Internal medicine Neuropilin medicine Humans Receptors Growth Factor Enzyme Inhibitors Growth Substances Molecular Biology Cells Cultured Protein Kinase C Protein kinase C Lymphokines Vascular Endothelial Growth Factor Receptor-1 Tumor Necrosis Factor-alpha Vascular Endothelial Growth Factors Chemistry Receptor Protein-Tyrosine Kinases Drug Synergism Kinase insert domain receptor Cell Biology Protein-Tyrosine Kinases Staurosporine Genistein Molecular biology Up-Regulation Vascular endothelial growth factor Vascular endothelial growth factor A Receptors Vascular Endothelial Growth Factor Endocrinology Mutation cardiovascular system Tumor necrosis factor alpha Endothelium Vascular Signal transduction Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 276:5281-5286 |
| ISSN: | 0021-9258 |
| Popis: | Vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-alpha) have been shown to synergistically increase tissue factor (TF) expression in endothelial cells; however, the role of the VEGF receptors (KDR, Flt-1, and neuropilin) in this process is unclear. Here we report that VEGF binding to the KDR receptor is necessary and sufficient for the potentiation of TNF-induced TF expression in human umbilical vein endothelial cells. TF expression was evaluated by Western blot analysis and fluorescence-activated cell sorting. In the absence of TNF-alpha, wild-type VEGF- or KDR receptor-selective variants induced an approximate 7-fold increase in total TF expression. Treatment with TNF alone produced an approximate 110-fold increase in total TF expression, whereas coincubation of TNF-alpha with wild-type VEGF- or KDR-selective variants resulted in an approximate 250-fold increase in TF expression. VEGF lacking the heparin binding domain was also able to potentiate TF expression, indicating that heparin-sulfate proteoglycan or neuropilin binding is not required for TF up-regulation. Neither placental growth factor nor an Flt-1-selective variant was capable of inducing TF expression in the presence or absence of TNF. Inhibition of protein-tyrosine kinase or protein kinase C activity significantly blocked the TNF/VEGF potentiation of TF up-regulation, whereas phorbol 12-myristate 13-acetate, a protein kinase C activator, increased TF expression. These data demonstrate that KDR receptor signaling governs both VEGF-induced TF expression and the potentiation of TNF-induced up-regulation of TF. |
| Databáze: | OpenAIRE |
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