Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinase pathway by a novel mitogen-activated protein kinase phosphatase

Kenji Ashida, Kiminobu Goto, Yue Zhao, Taijiro Okabe, Toshihiko Yanase, Ryoichi Takayanagi, Masatoshi Nomura, Hajime Nawata

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Dehydroepiandrosterone-sulfate, the sulfated form of dehydroepiandrosterone, is the most abundant steroid in young adults, but gradually declines with aging. In humans, the clinical application of dehydroepiandrosterone targeting some collagen diseases, such as systemic lupus erythematosus, as an adjunctive treatment has been applied in clinical trial. Here, we report that dehydroepiandrosterone may negatively regulate the mitogen-activated protein kinase pathway in humans via a novel dual specificity protein phosphatase, DDSP (dehydroepiandrosterone-enhanced dual specificity protein phosphatase). DDSP is highly homologous to LCPTP/HePTP, a tissue-specific protein tyrosine phosphatase (PTP) which negatively regulates both ERK and p38-mitogen-activated protein kinase, and is transcribed from the PTPN7 locus by alternative splicing. Although previous reports have shown that the mRNA expression of the LCPTP/HePTP gene was inducible by extracellular signals such as T-cell antigen receptor stimulation, reverse transcribed (RT)-PCR experiments using specific sets of primers suggested that the expression of LCPTP/HePTP was constitutive while the actual inducible sequence was that of DDSP. Furthermore DDSP was widely distributed among different types of human tissues and specifically interacted with p38-mitogen-activated protein kinase. This inducible negative regulation of the p38-mitogen-activated protein kinase-dependent pathway may help to clarify the broad range of dehydroepiandrosterone actions, thereby aiding the development of new preventive or adjunctive applications for human diseases.

Original languageEnglish
Pages (from-to)84-94
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1728
Issue number1-2
DOIs
Publication statusPublished - Apr 5 2005

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Mitogen-Activated Protein Kinase Phosphatases
Dehydroepiandrosterone
p38 Mitogen-Activated Protein Kinases
Dual-Specificity Phosphatases
Phosphoprotein Phosphatases
Tissue
Collagen Diseases
Dehydroepiandrosterone Sulfate
Protein Tyrosine Phosphatases
Alternative Splicing
T-Cell Antigen Receptor
Mitogen-Activated Protein Kinases
Systemic Lupus Erythematosus
Young Adult
Collagen
Genes
Aging of materials
Steroids
Clinical Trials
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

Cite this

Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinase pathway by a novel mitogen-activated protein kinase phosphatase. / Ashida, Kenji; Goto, Kiminobu; Zhao, Yue; Okabe, Taijiro; Yanase, Toshihiko; Takayanagi, Ryoichi; Nomura, Masatoshi; Nawata, Hajime.

In: Biochimica et Biophysica Acta - Gene Structure and Expression, Vol. 1728, No. 1-2, 05.04.2005, p. 84-94.

Research output: Contribution to journalArticle

Ashida, Kenji ; Goto, Kiminobu ; Zhao, Yue ; Okabe, Taijiro ; Yanase, Toshihiko ; Takayanagi, Ryoichi ; Nomura, Masatoshi ; Nawata, Hajime. / Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinase pathway by a novel mitogen-activated protein kinase phosphatase. In: Biochimica et Biophysica Acta - Gene Structure and Expression. 2005 ; Vol. 1728, No. 1-2. pp. 84-94.
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