jkk-1 and mek-1 regulate body movement coordination and response to heavy metals through jnk-1 in Caenorhabditis elegans.
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-1 alpha and JNK-1 beta. 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.
Villanueva
A
A
Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Lozano
J
J
Morales
A
A
Lin
X
X
Deng
X
X
Hengartner
M O
MO
Kolesnick
R N
RN
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002478:Cells, Cultured; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D008124:Locomotion; D048369:MAP Kinase Kinase 1; D019216:Metals, Heavy / Q000494:pharmacology*; D048055:Mitogen-Activated Protein Kinase 8; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D018510:RNA, Helminth / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D013312:Stress, Physiological; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D019216:Metals, Heavy; D018510:RNA, Helminth; D005680:gamma-Aminobutyric Acid; D011494:Protein Kinases; C120814:jkk-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C437322:JNK-1 protein, C elegans; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases