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Suppression of activated Let-60 ras prot ... inase in vulval differentiation
Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegans Sur-1 MAP kinase in vulval differentiation.
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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.
Wu Y, Han M
Genes & development
1994-01-01 00:00
8
2
147-59
ATP-Binding Cassette Transporters,Amino Acid Sequence,Animals,Base Sequence,Caenorhabditis elegans,Caenorhabditis elegans Proteins,Cell Differentiation,Cloning, Molecular,DNA, Complementary,Embryonic Induction,Female,Genes, ras,Helminth Proteins,Humans,Mitogen-Activated Protein Kinase 1,Molecular Sequence Data,Multidrug Resistance-Associated Proteins,Phenotype,Protein-Serine-Threonine Kinases,Protein-Tyrosine Kinases,Sequence Homology, Amino Acid,Signal Transduction,Suppression, Genetic,Vulva,ras Proteins,ATP-Binding Cassette Transporters,Abcc8 protein, rat,Caenorhabditis elegans Proteins,DNA, Complementary,Helminth Proteins,Multidrug Resistance-Associated Proteins,let-60 protein, C elegans,Protein-Tyrosine Kinases,Mitogen-Activated Protein Kinase 1,Protein-Serine-Threonine Kinases,ras Proteins
Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder 80309-0347
Genes Dev.
NIGMS R01 GM47869
0890-9369
513
True
8299935
