jkk-1 and mek-1 regulate body movement coordination and response to heavy metals through jnk-1 in Caenorhabditis elegans Journal Article

Authors: Villanueva, A.; Lozano, J.; Morales, A.; Lin, X.; Deng, X.; Hengartner, M. O.; Kolesnick, R. N.
Article Title: jkk-1 and mek-1 regulate body movement coordination and response to heavy metals through jnk-1 in Caenorhabditis elegans
Abstract: Although in vitro evidence suggests two c-Jun N-terminal kinase (JNK) kinases, MKK4 and MKK7, transactivate JNK, in vivo confirmation is incomplete. In fact, JNK deficiency may differ from the composite deficiency of MKK4 and MKK7 in Drosophila and mice. Recently, the Caenorhabditis elegans homolog of human JNK, jnk-1, and two MKK-7s, mek-1 and jkk-1, were cloned. Here we characterize jnk-1, which encodes two isoforms JNK-1α and JNK-1β. A null allele,jnk-1(gk7), yielded worms with defective body movement coordination and modest mechanosensory deficits. Similarly to jkk-1 mutants, elimination of GABAergic signals suppressed the jnk-1(gk7) locomotion defect. Like mek-1 nulls, jnk-1(gk7) showed copper and cadmium hypersensitivity. Conditional expression of JNK-1 isoforms rescued these defects, suggesting that they are not due to developmental errors. While jkk-1 or mek-1 inactivation mimicked jnk-1(gk7) locomotion and heavy metal stress defects, respectively, mkk-4 inactivation did not, but rather yielded defective egg laying. Our results delineate at least two different JNK pathways through jkk-1 and mek-1 in C.elegans, and define interaction between MKK7, but not MKK4, and JNK.
Keywords: unclassified drug; mutation; nonhuman; animals; allele; cells, cultured; protein kinases; stress activated protein kinase; drosophila; amino acid sequence; molecular sequence data; sequence homology, amino acid; protein-serine-threonine kinases; gamma-aminobutyric acid; alternative splicing; stress; caenorhabditis elegans; worm; rna, helminth; mitogen-activated protein kinases; mitogen activated protein kinase kinase; mitogen-activated protein kinase kinases; map kinase kinase 1; copper; locomotion; behavior, animal; motor coordination; mitogen-activated protein kinase 8; caenorhabditis elegans proteins; hypersensitivity; cadmium; stress activated protein kinase 1; helminth proteins; heavy metal; egg laying; priority journal; article; body movement; heavy metals; jkk-1; mek-1; c jun n terminal kinase 1 alpha; c jun n terminal kinase 1 beta; jkk 1; mek 1; mkk 4; mkk 7; metals, heavy
Journal Title: EMBO Journal
Volume: 20
Issue: 18
ISSN: 0261-4189
Publisher: Wiley Blackwell  
Date Published: 2001-09-17
Start Page: 5114
End Page: 5128
Language: English
DOI: 10.1093/emboj/20.18.5114
PUBMED: 11566876
PROVIDER: scopus
PMCID: PMC125628
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Xinhua Lin
    6 Lin
  2. Jose Lozano
    8 Lozano
  3. Richard N Kolesnick
    235 Kolesnick
  4. Xinzhu Deng
    10 Deng