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.

摘要: Proliferation of endothelial cells is regulated by angiogenic and antiangiogenic factors whose actions are mediated complex interactions multiple signaling pathways. Both vascular growth factor (VEGF) basic fibroblast (bFGF) stimulate cell proliferation activate the mitogen-activated protein kinase (MAPK) cascade in bovine brain capillary (BBE) cells. We have extended these findings to show that both mitogens MAPK via stimulation Raf-3. Activation Raf/MAPK inhibited increasing intracellular cAMP levels pharmacologically or endogenously expressed beta-adrenergic receptors. VEGF- bFGF-induced Raf-1 activity blocked presence forskolin 8-bromo-cAMP 80%. The increased appear be cAMP-dependent (PKA), since treatment with H-89, a specific inhibitor PKA, reversed inhibitory effect elevated on mitogen-induced activation. Moreover, elevations cAMP/PKA inhibit proliferation. These demonstrate, cultured cells, pathway potentially an important physiological mitogen activation