Premium
The Caenorhabditis elegans MAPK phosphatase VHP‐1 mediates a novel JNK‐like signaling pathway in stress response
Author(s) -
Mizuno Tomoaki,
Hisamoto Naoki,
Terada Takashi,
Kondo Tae,
Adachi Makoto,
Nishida Eisuke,
Kim Dennis H,
Ausubel Frederick M,
Matsumoto Kunihiro
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600226
Subject(s) - caenorhabditis elegans , mapk/erk pathway , biology , microbiology and biotechnology , phosphatase , kinase , dual specificity phosphatase , p38 mitogen activated protein kinases , map kinase kinase kinase , protein phosphatase 2 , protein kinase a , signal transduction , mitogen activated protein kinase , mitogen activated protein kinase kinase , phosphorylation , genetics , gene
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.