title: DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression.
abstract: The dual-specificity phosphatase (DUSP) 13 gene encodes two atypical DUSPs, DUSP13B/TMDP and DUSP13A/MDSP using alternative exons. DUSP13B protein is most highly expressed in testis, particularly in spermatocytes and round spermatids of the seminiferous tubules, while that of DUSP13A is restricted to skeletal muscle. Here, we show that DUSP13B inactivated MAPK activation in the order of selectivity, JNK = p38>ERK in cells, while DUSP13A did not show MAPK phosphatase activity. Reporter gene analysis showed that DUSP13B had significant inhibitory effect on AP-1-dependent gene expression, but DUSP13A did not. To our knowledge, DUSP13B is the first identified testis-specific phosphatase that inhibits stress-activated MAPKs. These data suggest an important role for DUSP13B in protection from external stress during spermatogenesis.
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Medeshima-Shiode, Natori, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Katagiri
authors.forename: Kouhei
authors.initials: K
authors.lastname: Masuda
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nomura
authors.forename: Kan
authors.initials: K
authors.lastname: Tanoue
authors.forename: Shoko
authors.initials: S
authors.lastname: Fujita
authors.forename: Yoji
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Katakura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Shiiba
authors.forename: Eiki
authors.initials: E
authors.lastname: Nomura
authors.forename: Masami
authors.initials: M
authors.lastname: Sato
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tanuma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shima
mesh_terms: D000818:Animals; D002460:Cell Line; D054637:Dual-Specificity Phosphatases / Q000502:physiology*; D004789:Enzyme Activation; D005091:Exons; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000502:physiology*
chemical_list: D054637:Dual-Specificity Phosphatases; D020928:Mitogen-Activated Protein Kinases; D047428:Protein Kinase Inhibitors; D018808:Transcription Factor AP-1; C498627:DUSP13B protein, human