title: Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegans Sur-1 MAP kinase in vulval differentiation.
abstract: The let-60 ras gene of Caenorhabditis elegans is one of the key players in a signal transduction pathway that controls the choice between vulval and epidermal differentiation in response to extracellular signals. To identify components acting downstream of let-60 ras in the vulval signaling pathway, we have identified a reduction-of-function mutation in the sur-1 gene that completely suppresses the multivulva phenotype of a hyperactive let-60 ras mutation. About 10% of animals homozygous for the sur-1 mutation also display a specific and intriguing vulval cell lineage defect. In addition, the sur-1 mutation results in a cold-sensitive egg-laying defective phenotype and a partial larval lethal phenotype. We have cloned the sur-1 gene by DNA-mediated transformation and have shown that it encodes a protein similar in overall structure to mammalian MAP kinases (ERKs). The functional homology between Sur-1 MAP kinase and mammalian MAP kinases was also demonstrated by the ability of a rat ERK2 kinase to rescue the sur-1 mutant phenotypes. Genetic double-mutant analyses place sur-1 downstream of let-60 ras but upstream of lin-1 in the vulval signaling pathway. Our results provide further evidence for the extreme conservation of Ras-mediated signaling pathway between worms and humans and for the function of MAP kinases in cell signaling processes that control cell differentiation and animal development.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder 80309-0347.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Han
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002454:Cell Differentiation / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004627:Embryonic Induction / Q000235:genetics; D005260:Female; D011905:Genes, ras; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011955:Receptors, Drug; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D064233:Sulfonylurea Receptors; D013489:Suppression, Genetic; D014844:Vulva / Q000166:cytology*; D018631:ras Proteins
chemical_list: D018528:ATP-Binding Cassette Transporters; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D015801:Helminth Proteins; D019950:Mitogen-Activated Protein Kinase 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D018631:ras Proteins; C577507:ABCC8 protein, human; C577509:Abcc8 protein, rat; C066646:let-60 protein, C elegans