Divergence in signaling pathways involved in promotion of cell viability mediated by bFGF, NGF, and EGF in PC12 cells.
We employed a series of inhibitors of intracellular cascade to disclose the precise molecular mechanisms by which basic fibroblast growth factor (bFGF) promotes viability of PC12 cells and compared with nerve growth factor (NGF) and epidermal growth factor (EGF). The MEK 1 and 2 inhibitors, U0126 and PD98059, significantly suppressed cell viability mediated by bFGF in a dose-dependent manner, and to a greater extent compared with EGF and NGF. The degree of MEK dependency for growth factor-mediated cell viability was estimated to be in the order of bFGF, EGF, and NGF. Rapamycin strongly inhibited the effect of NGF on cell viability, compared with bFGF and EGF. The mechanisms of action of NGF-mediated cell viability may depend largely on p70 S6 kinase-related signal transduction pathways comparing to bFGF and EGF. The present findings suggest that different signal transduction systems may be involved in the molecular mechanisms by which bFGF, NGF, and EGF mediate cell viability.
Kawamata
Takakazu
T
Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan. tkawamata@nij.twmu.ac.jp
Yamaguchi
Tomoko
T
Shin-ya
Kazuo
K
Hori
Tomokatsu
T
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D016716:PC12 Cells; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology
D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009570:Nitriles; D000081082:Phosphoinositide-3 Kinase Inhibitors; C113580:U 0126; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus