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| Subject Categories: Signal Transduction |
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| The EMBO Journal
(2004) 23, 2226–2234, doi:10.1038/sj.emboj.7600226 Published online 29 April 2004 |
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| The Caenorhabditis elegans MAPK phosphatase VHP-1 mediates a novel JNK-like signaling pathway in stress response |
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| Tomoaki Mizuno1, 2, Naoki Hisamoto1, 2, Takashi Terada1, 2, Tae Kondo1, 2, Makoto Adachi3, Eisuke Nishida3, Dennis H Kim4, 5, Frederick M Ausubel4, 5 and Kunihiro Matsumoto1, 2 |
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1 Department of Molecular Biology, Graduate School of Science, Institute for Advanced Research, Nagoya University, Nagoya, Japan 2 CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya, Japan 3 Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan 4 Department of Genetics, Harvard Medical School, Boston, MA, USA 5 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA To whom correspondence should be addressed Kunihiro Matsumoto, Department of Molecular Biology, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan. Tel.: +81 52 789 3000; Fax: +81 52 789 2589 or 3001; E-mail: g44177a@nucc.cc.nagoya-u.ac.jp Received 1 March 2004; Accepted 7 April 2004; Published online 29 April 2004. |
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| Abstract |
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| Mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli and to a wide variety of environmental stresses. MAPK cascades can be inactivated at the MAPK activation step by members of the MAPK phosphatase (MKP) family. However, the components that act in MKP-regulated pathways have not been well characterized in the context of whole organisms. Here we characterize the Caenorhabditis elegans vhp-1 gene, encoding an MKP that acts preferentially on the c-Jun N-terminal kinase (JNK) and p38 MAPKs. We found that animals defective in vhp-1 are arrested during larval development. This vhp-1 defect is suppressed by loss-of-function mutations in the kgb-1, mek-1, and mlk-1 genes encoding a JNK-like MAPK, an MKK7-type MAPKK, and an MLK-type MAPKKK, respectively. The genetic and biochemical data presented here demonstrate a critical role for VHP-1 in the KGB-1 pathway. Loss-of-function mutations in each component in the KGB-1 pathway result in hypersensitivity to heavy metals. These results suggest that VHP-1 plays a pivotal role in the integration and fine-tuning of the stress response regulated by the KGB-1 MAPK pathway. |
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| Keywords: C. elegans, heavy metal stress, MAP kinase, MAPK phosphatase |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHA GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins Nature Immunology Article (01 Jun 2001) The EMBO Journal Article (17 Sep 2001) The C.elegans MAPK phosphatase LIP-1 is required for the G 2 /M meiotic arrest of developing oocytes The EMBO Journal Article (15 Aug 2002) A Caenorhabditis elegans MAP kinase kinase, MEK-1, is involved in stress responses The EMBO Journal Article (02 Oct 2000) |
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