cAMP-dependent protein kinase inhibits the mitogenic action of vascular endothelial growth factor and fibroblast growth factor in capillary endothelial cells by blocking Raf activation
| Autor: | Hsinyu Lee, Richard I. Weiner, Gisela D'Angelo |
|---|---|
| Přispěvatelé: | Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Vascular Endothelial Growth Factor A
MAPK/ERK pathway MESH: Signal Transduction Phosphodiesterase Inhibitors [SDV]Life Sciences [q-bio] Basic fibroblast growth factor MESH: Sulfonamides 8-Bromo Cyclic Adenosine Monophosphate MESH: Adenylyl Cyclases Endothelial Growth Factors MAPK cascade Fibroblast growth factor MESH: Vascular Endothelial Growth Factors Biochemistry MESH: Phosphodiesterase Inhibitors MESH: Isoproterenol chemistry.chemical_compound MESH: Endothelial Growth Factors 1-Methyl-3-isobutylxanthine MESH: 8-Bromo Cyclic Adenosine Monophosphate Cyclic AMP MESH: Animals Enzyme Inhibitors 10. No inequality Cells Cultured MESH: Cyclic AMP Lymphokines Sulfonamides Vascular Endothelial Growth Factors MESH: 1-Methyl-3-isobutylxanthine Brain Cell biology Vascular endothelial growth factor A MESH: Cattle Vascular endothelial growth factor C MESH: Enzyme Inhibitors MESH: Cell Division Fibroblast Growth Factor 2 MESH: Endothelium Vascular Cell Division Adenylyl Cyclases Signal Transduction MESH: Cells Cultured MESH: Colforsin MESH: Cyclic AMP-Dependent Protein Kinases Vascular endothelial growth inhibitor MESH: Brain MESH: Calcium-Calmodulin-Dependent Protein Kinases MESH: Isoquinolines Animals Protein kinase A Molecular Biology MESH: Capillaries MESH: Lymphokines MESH: Fibroblast Growth Factor 2 MESH: Vascular Endothelial Growth Factor A Colforsin Isoproterenol Cell Biology Isoquinolines Cyclic AMP-Dependent Protein Kinases Capillaries Proto-Oncogene Proteins c-raf chemistry Calcium-Calmodulin-Dependent Protein Kinases MESH: Proto-Oncogene Proteins c-raf Cattle Endothelium Vascular |
| Zdroj: | Journal of Cellular Biochemistry Journal of Cellular Biochemistry, Wiley, 1997, 67 (3), pp.353-66 HAL |
| ISSN: | 0730-2312 1097-4644 |
| Popis: | International audience; Proliferation of endothelial cells is regulated by angiogenic and antiangiogenic factors whose actions are mediated by complex interactions of multiple signaling pathways. Both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) stimulate cell proliferation and activate the mitogen-activated protein kinase (MAPK) cascade in bovine brain capillary endothelial (BBE) cells. We have extended these findings to show that both mitogens activate MAPK via stimulation of Raf-3. Activation of Raf/MAPK is inhibited by increasing intracellular cAMP levels pharmacologically or via stimulation of endogenously expressed beta-adrenergic receptors. Both VEGF- and bFGF-induced Raf-1 activity are blocked in the presence of forskolin or 8-bromo-cAMP by 80%. The actions of increased cAMP appear to be mediated by cAMP-dependent protein kinase (PKA), since treatment with H-89, a the specific inhibitor of PKA, reversed the inhibitory effect of elevated cAMP levels on mitogen-induced cell proliferation and Raf/MAPK activation. Moreover, elevations in cAMP/PKA activity inhibit mitogen-induced cell proliferation. These findings demonstrate, in cultured endothelial cells, that the cAMP/PKA signaling pathway is potentially an important physiological inhibitor of mitogen activation of the MAPK cascade and cell proliferation. |
| Databáze: | OpenAIRE |
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