PMID- 15777705
OWN - NLM
STAT- MEDLINE
DCOM- 20050524
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1728
IP  - 1-2
DP  - 2005 Apr 5
TI  - Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein 
      kinase pathway by a novel mitogen-activated protein kinase phosphatase.
PG  - 84-94
AB  - 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.
FAU - Ashida, Kenji
AU  - Ashida K
AD  - Department of Medicine and Bioregulatory Science (3rd Department of Internal 
      Medicine), Graduate School of Medical Sciences, Kyushu University, Maidashi 
      3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
FAU - Goto, Kiminobu
AU  - Goto K
FAU - Zhao, Yue
AU  - Zhao Y
FAU - Okabe, Taijiro
AU  - Okabe T
FAU - Yanase, Toshihiko
AU  - Yanase T
FAU - Takayanagi, Ryoichi
AU  - Takayanagi R
FAU - Nomura, Masatoshi
AU  - Nomura M
FAU - Nawata, Hajime
AU  - Nawata H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.- (DDSP protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Baculoviridae
MH  - Base Sequence
MH  - Blotting, Western
MH  - DNA Primers
MH  - DNA, Complementary/genetics
MH  - Dehydroepiandrosterone/*metabolism
MH  - *Gene Expression Regulation, Enzymologic
MH  - Genetic Vectors
MH  - Glutathione Transferase
MH  - Humans
MH  - Immunoprecipitation
MH  - Mice
MH  - Molecular Sequence Data
MH  - NIH 3T3 Cells
MH  - Protein Tyrosine Phosphatases/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Analysis, DNA
MH  - Signal Transduction/*physiology
MH  - Tumor Cells, Cultured
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2005/03/22 09:00
MHDA- 2005/05/25 09:00
CRDT- 2005/03/22 09:00
PHST- 2004/05/10 00:00 [received]
PHST- 2005/01/10 00:00 [revised]
PHST- 2005/01/26 00:00 [accepted]
PHST- 2005/03/22 09:00 [pubmed]
PHST- 2005/05/25 09:00 [medline]
PHST- 2005/03/22 09:00 [entrez]
AID - S0167-4781(05)00037-0 [pii]
AID - 10.1016/j.bbaexp.2005.01.016 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2005 Apr 5;1728(1-2):84-94. doi: 
      10.1016/j.bbaexp.2005.01.016.