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jkk‐1 and mek‐1 regulate body movement coordination and response to heavy metals through jnk‐1 in Caenorhabditis elegans
Author(s) -
Villanueva Alberto,
Lozano José,
Morales Albert,
Lin Xinhua,
Deng Xinzhu,
Hengartner Michael O.,
Kolesnick Richard N.
Publication year - 2001
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 - 10.1093/emboj/20.18.5114
Subject(s) - caenorhabditis elegans , biology , kinase , microbiology and biotechnology , mitogen activated protein kinase , gene isoform , genetics , gene
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.