Hypertrophic Agonists Stimulate the Activities of the Protein Kinases c-Raf and A-Raf in Cultured Ventricular Myocytes

摘要: We detected expression of two Raf isoforms, c-Raf and A-Raf, in neonatal rat heart. Both isoforms phosphorylated, activated, formed complexes with mitogen-activated protein kinase 1 vitro. However, these were differentially activated by hypertrophic stimuli such as peptide growth factors, endothelin-1 (ET1), or 12-O-tetradecanoylphorbol-13-acetate (TPA) that activate the cascade. Exposure cultured ventricular myocytes to acidic fibroblast factor but not A-Raf. In contrast, TPA produced a sustained activation A-Raf only transiently c-Raf. ET1 both isoforms. most potent activators utilized C-dependent pathways, stimulation was also partially sensitive pertussis toxin pretreatment. inhibited cAMP-dependent although less affected. Fetal calf serum, phenylephrine, carbachol These results demonstrate are regulated may be an important mediator cascade when cAMP is elevated.