The mitogen-activated protein kinase cascade mediates neurotrophic effect of epidermal growth factor in cultured rat hippocampal neurons.
Epidermal growth factor (EGF) has been reported to support the survival of cultured brain neurons. In the present study, we investigated whether the neurotrophic effect of EGF is mediated by the mitogen-activated protein kinase (MAPK) cascade in cultured rat hippocampal neurons. Recombinant human EGF (0.1-10 ng/ml) induced phosphorylation of p44/42 MAPK (ERK1/2) in a concentration-and time-dependent manner. EGF-induced ERK1/2 phosphorylation and promotion of neuronal survival were both blocked by U0126 and PD98059, inhibitors of the MAPK-activating enzyme MEK. These results suggest that the MEK/ERK signal transduction cascade is involved in the neurotrophic effect of EGF.
Abe
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. kazuhoab@mol.f.u-tokyo.ac.jp
Saito
H
H
D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D048369:MAP Kinase Kinase 1; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011799:Quinazolines; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D020032:Tyrphostins / Q000494:pharmacology
D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009570:Nitriles; D011799:Quinazolines; D011994:Recombinant Proteins; D020032:Tyrphostins; C113580:U 0126; C101044:RTKI cpd; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D017027:Protein Tyrosine Phosphatases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one