TY - JOUR
T1 - Ras/MEK pathway is required for NGF-induced expression of tyrosine hydroxylase gene
AU - Suzuki, Takahiro
AU - Kurahashi, Hiroki
AU - Ichinose, Hiroshi
N1 - Funding Information:
This work was supported by grants from the programs Grants-in-Aid for Encouragement of Young Scientists (to T.S.) and Grants-in-Aid for Scientific Research on Priority Areas (C)—Advanced Brain Science Project—(to H.I.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Health Science Research Grants—Research on Human Genome, Tissue Engineering, Food Biotechnology—from the Ministry of Health, Labour and Welfare of Japan (to H.I.); and by the Human Frontier Science Program (to H.I.); Grants-in-Aid for Bio-venture Research Center of Fujita Health University from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Fujita Health University.
PY - 2004/3/5
Y1 - 2004/3/5
N2 - Neurotrophins are essential for the development and survival of catecholaminergic neurons. However, the critical pathway for expression of the tyrosine hydroxylase (TH) gene induced by neurotrophin is still unclear. Here we found that Ras/MEK pathway is required for NGF-induced expression of the TH gene in PC12D cells. Induction of TH mRNA by NGF was abolished by pretreatment of the cells with U0126, an inhibitor for MEK1/2, but not with inhibitors for p38 MAPK, PI3K, and PKA. U0126 inhibited TH promoter activity at the same concentration as it acted on ERK1/2 phosphorylation. A dominant-negative form of Ras suppressed the NGF-induced activation of the TH reporter gene, and transient transfection of cells with wild-type Ras and an active form of MEK1 increased the TH promoter activity. The reporter assay also demonstrated that the Ras/MEK pathway acted on both the AP-1-binding motif and the cAMP-responsive element in the TH promoter.
AB - Neurotrophins are essential for the development and survival of catecholaminergic neurons. However, the critical pathway for expression of the tyrosine hydroxylase (TH) gene induced by neurotrophin is still unclear. Here we found that Ras/MEK pathway is required for NGF-induced expression of the TH gene in PC12D cells. Induction of TH mRNA by NGF was abolished by pretreatment of the cells with U0126, an inhibitor for MEK1/2, but not with inhibitors for p38 MAPK, PI3K, and PKA. U0126 inhibited TH promoter activity at the same concentration as it acted on ERK1/2 phosphorylation. A dominant-negative form of Ras suppressed the NGF-induced activation of the TH reporter gene, and transient transfection of cells with wild-type Ras and an active form of MEK1 increased the TH promoter activity. The reporter assay also demonstrated that the Ras/MEK pathway acted on both the AP-1-binding motif and the cAMP-responsive element in the TH promoter.
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U2 - 10.1016/j.bbrc.2004.01.068
DO - 10.1016/j.bbrc.2004.01.068
M3 - Article
C2 - 14766220
AN - SCOPUS:0842267445
VL - 315
SP - 389
EP - 396
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -