{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:06:22Z","timestamp":1790003182870,"version":"4.0.1"},"reference-count":56,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1995,3,15]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1101\/gad.9.6.742","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T21:15:46Z","timestamp":1181078146000},"page":"742-755","source":"Crossref","is-referenced-by-count":86,"title":["MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions in Ras-mediated vulval induction and other developmental events."],"prefix":"10.1101","volume":"9","author":[{"given":"Y","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K L","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1995,3,15]]},"reference":[{"key":"2021111418212873000_9.6.742.1","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(92)90131-U"},{"key":"2021111418212873000_9.6.742.2","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1002\/j.1460-2075.1994.tb06424.x","article-title":"Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-l.","volume":"13","year":"1994","journal-title":"EMBO J."},{"key":"2021111418212873000_9.6.742.3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/genetics\/128.2.251","article-title":"Multiple functions of let-23, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction.","volume":"128","year":"1991","journal-title":"Genetics"},{"key":"2021111418212873000_9.6.742.4","doi-asserted-by":"publisher","DOI":"10.1038\/348693a0"},{"key":"2021111418212873000_9.6.742.5","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(94)90147-3"},{"key":"2021111418212873000_9.6.742.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.2164259"},{"key":"2021111418212873000_9.6.742.7","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(91)01013-R"},{"key":"2021111418212873000_9.6.742.8","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/20031967725"},{"key":"2021111418212873000_9.6.742.9","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1242\/dev.118.2.297","article-title":"Multiple cell interactions are required for fate specification during male spicule development in Caenorhabditis elegans.","volume":"118","year":"1993","journal-title":"Development"},{"key":"2021111418212873000_9.6.742.10","doi-asserted-by":"crossref","unstructured":"Church, D.L., Guan, K.L. and Lambie. E.J. 1995. mek-2, mpk-1\/sur-1 and let60 ras are required for meiotic cell cycle progression in C. elegans. 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