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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1995-6-1
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pubmed:databankReference |
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pubmed:abstractText |
Activated Ras initiates a cascade of sequential phosphorylation events, including the protein kinases Raf, MEK, and MAP kinase. The Let-60 Ras-mediated signal transduction pathway controls vulval induction in Caenorhabditis elegans. Both Lin-45 Raf and Sur-1 MAP kinase have been determined to be essential factors during vulval induction; however, the C. elegans mek gene has not been identified. In this paper, we have cloned a C. elegans mek gene, mek-2, and demonstrated that the MEK-2 protein possesses the biochemical properties of MAP kinase kinases: The C. elegans MEK-2 protein can phosphorylate and activate a human MAP kinase (ERK1), and MEK-2 itself can be phosphorylated and activated by immunoprecipitated mammalian Raf. The mek-2 gene plays a key role in the let-60 ras-mediated vulval induction pathway, as loss-of-function mutations in the gene (ku114 and h294) significantly reduce the signal transmitted through Ras. mek-2(ku114) completely suppressed the Multivulva (Muv) phenotype of a hyperactive let-60 ras mutation, and animals homozygous for mek-2(ku114) also displayed a partial larval lethal phenotype. Animals homozygous for mek-2(h294) exhibited a highly penetrant sterile and Vulvaless phenotype. Microinjection of a gain-of-function mek-2 mutation resulted in Muv and other mutant phenotypes, whereas microinjection of a dominant-negative mutation not only suppressed the Muv phenotype of an activated let-60 ras mutation but also caused an egg-laying defective phenotype in otherwise wild type animals. Our results demonstrate that mek-2 acts between lin-45 raf and sur-1/mpk-1 in a signal transduction pathway used in the control of vulval differentiation and other developmental events.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Glycosyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SUR1 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0890-9369
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
742-55
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7729690-Amino Acid Sequence,
pubmed-meshheading:7729690-Animals,
pubmed-meshheading:7729690-Base Sequence,
pubmed-meshheading:7729690-Caenorhabditis elegans,
pubmed-meshheading:7729690-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:7729690-Cell Communication,
pubmed-meshheading:7729690-Cell Differentiation,
pubmed-meshheading:7729690-DNA, Complementary,
pubmed-meshheading:7729690-Embryonic Induction,
pubmed-meshheading:7729690-Female,
pubmed-meshheading:7729690-Genes, Helminth,
pubmed-meshheading:7729690-Glycosyltransferases,
pubmed-meshheading:7729690-MAP Kinase Kinase 2,
pubmed-meshheading:7729690-Membrane Proteins,
pubmed-meshheading:7729690-Microinjections,
pubmed-meshheading:7729690-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:7729690-Molecular Sequence Data,
pubmed-meshheading:7729690-Protein-Serine-Threonine Kinases,
pubmed-meshheading:7729690-Protein-Tyrosine Kinases,
pubmed-meshheading:7729690-Proto-Oncogene Proteins,
pubmed-meshheading:7729690-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:7729690-Repressor Proteins,
pubmed-meshheading:7729690-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:7729690-Sequence Homology, Amino Acid,
pubmed-meshheading:7729690-Signal Transduction,
pubmed-meshheading:7729690-Vulva,
pubmed-meshheading:7729690-ras Proteins
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pubmed:year |
1995
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pubmed:articleTitle |
MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions in Ras-mediated vulval induction and other developmental events.
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pubmed:affiliation |
Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder 80309, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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