Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 389-396 |
| Number of pages | 8 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 315 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 05-03-2004 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
}
Ras/MEK pathway is required for NGF-induced expression of tyrosine hydroxylase gene. / Suzuki, Takahiro; Kurahashi, Hiroki; Ichinose, Hiroshi.
In: Biochemical and Biophysical Research Communications, Vol. 315, No. 2, 05.03.2004, p. 389-396.Research output: Contribution to journal › Article
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
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.
UR - http://www.scopus.com/inward/record.url?scp=0842267445&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0842267445&partnerID=8YFLogxK
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 -