Ras/MEK pathway is required for NGF-induced expression of tyrosine hydroxylase gene

Takahiro Suzuki, Hiroki Kurahashi, Hiroshi Ichinose

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 languageEnglish
Pages (from-to)389-396
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume315
Issue number2
DOIs
Publication statusPublished - 05-03-2004

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Mitogen-Activated Protein Kinase Kinases
Tyrosine 3-Monooxygenase
Nerve Growth Factor
Genes
Nerve Growth Factors
Phosphorylation
Critical Pathways
Transcription Factor AP-1
p38 Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Reporter Genes
Neurons
Transfection
Assays
Chemical activation
Cells
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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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.",
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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 journalArticle

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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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