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| The EMBO Journal
(2000) 19, 5148–5156, doi:10.1093/emboj/19.19.5148 |
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| A Caenorhabditis elegans MAP kinase kinase, MEK-1, is involved in stress responses |
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| Makoto Koga1, 5, Richard Zwaal2, 3, 5, Kun-Liang Guan4, Leon Avery2 and Yasumi Ohshima1 |
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1 Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka 812-8581, Japan 2 Department of Biochemistry, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390-9148, USA 3 Present address: Devgen N.V., Technologiepark 9, Zwijnaarde B-9052, Belgium 4 Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48105, USA 5 M.Koga and R.Zwaal contributed equally to this work To whom correspondence should be addressed Yasumi Ohshima, yohshscb@mbox.nc.kyushu-u.ac.jp Received 4 April 2000; Revised 27 July 2000; Accepted 3 August 2000. |
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| Abstract |
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| The c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, was shown to be involved in the response to various stresses in cultured cells. However, there is little in vivo evidence indicating a role for a JNK pathway in the stress response of an organism. We identified the Caenorhabditis elegans mek-1 gene, which encodes a 347 amino acid protein highly homologous to mammalian MKK7, an activator of JNK. Mek-1 reporter fusion proteins are expressed in pharyngeal muscle, uterus, a portion of intestine, and neurons. A mek-1 deletion mutant is hypersensitive to copper and cadmium ions and to starvation. A wild-type mek-1 transgene rescued the hypersensitivity to the metal ions. Double mutants of mek-1 with an eat-5, eat-11 or eat-18 mutation, which are characterized by a limited feeding defect, showed distinct growth defects under normal conditions. Expression of an activated form of MEK-1 in the whole animal or specifically in the pharynx inhibited pharyngeal pumping. These results suggest a role for mek-1 in stress responses, with a focus in the pharynx and/or intestine. |
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| Keywords: Caenorhabditis elegans, heavy metal, MAP kinase kinase, starvation, stress response |
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