Synergistic activity of activin A and basic fibroblast growth factor on tyrosine hydroxylase expression through Smad3 and ERK1/ERK2 MAPK signaling pathways.
Activin has previously been shown to act as a nerve cell survival factor and to have neurotrophic effects on neurons. However, the role of activin in regulating neurotransmitter expression in the central nervous system and the exact mechanisms involved in this process are poorly understood. In the present study, we report that activin A and basic fibroblast growth factor (bFGF) synergistically increased the protein level of tyrosine hydroxylase (TH), and also greatly increased the TH mRNA level, in both mouse E14 striatal primary cell cultures and the hippocampal neuronal cell line HT22. Activin A and bFGF cooperatively stimulated nuclear translocation of Smad3 and specifically activated ERK1/2, but not p38 or JNK. Interestingly, a specific inhibitor for MEK, U0126, efficiently blocked the induction of TH promoter activity by activin A and bFGF, indicating that activin A collaborated with bFGF signaling to induce the TH gene through selective activation of ERK-type MAP kinase in mouse striatal and HT22 cells. These data suggest that activin A may act in concert with bFGF for the development of TH-positive neurons.
Bao
Y L
YL
Institute for Enzyme Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
Tsuchida
K
K
Liu
B
B
Kurisaki
A
A
Matsuzaki
T
T
Sugino
H
H
D028341:Activins / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D028322:Inhibin-beta Subunits / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051900:Smad3 Protein; D013268:Stimulation, Chemical; D015534:Trans-Activators / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D015534:Trans-Activators; C422405:activin A; D016222:Fibroblast Growth Factor 2; D028341:Activins; D028322:Inhibin-beta Subunits; D014446:Tyrosine 3-Monooxygenase