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  • The EMBO Journal (2000) 19, 5148 - 5156
  • doi:10.1093/emboj/19.19.5148

A Caenorhabditis elegans MAP kinase kinase, MEK-1, is involved in stress responses

Makoto Koga1,5, Richard Zwaal2,3,5, Kun-Liang Guan4, Leon Avery2 and Yasumi Ohshima1

  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

Correspondence to:

Yasumi Ohshima, E-mail: yohshscb@mbox.nc.kyushu-u.ac.jp

Received 4 April 2000; Accepted 3 August 2000; Revised 27 July 2000

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.

  • Keywords:

    • Caenorhabditis elegans,
    • heavy metal,
    • MAP kinase kinase,
    • starvation,
    • stress response