Ma. Bogoyevitch et al., HYPERTROPHIC AGONISTS STIMULATE THE ACTIVITIES OF THE PROTEIN-KINASESC-RAF AND A-RAF IN CULTURED VENTRICULAR MYOCYTES, The Journal of biological chemistry, 270(44), 1995, pp. 26303-26310
We detected expression of two Raf isoforms, c-Raf and A Raf, in neonat
al rat heart, Both isoforms phosphorylated, activated, and formed comp
lexes with mitogen-activated protein kinase kinase 1 in vitro. However
, these isoforms were differentially activated by hypertrophic stimuli
such as peptide growth factors, endothelin-l (ET1), or 12-O-tetradeca
noylphorbol-13-acetate (TPA) that activate the mitogen-activated prote
in kinase cascade, Exposure of cultured ventricular myocytes to acidic
fibroblast growth factor activated c-Raf but not A-Raf, In contrast,
TPA produced a sustained activation of A-Raf and only transiently acti
vated c-Raf. ET1 transiently activated both isoforms. TPA and ET1 were
the most potent activators of c-Raf and A-Raf. Both utilized protein
kinase C dependent pathways, but stimulation by ET1 was also partially
sensitive to pertussis toxin pretreatment. c-Raf was inhibited by act
ivation of cAMP-dependent protein kinase although A-Raf was less affec
ted. Fetal calf serum, phenylephrine, and carbachol were less potent a
ctivators of c-Raf and A-Raf. These results demonstrate that A-Raf and
c-Raf are differentially regulated and that A-Raf may be an important
mediator of mitogen activated protein kinase cas cade activation when
cAMP is elevated.