{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:00:22Z","timestamp":1779343222964,"version":"3.51.4"},"reference-count":68,"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>An evolutionarily conserved signal transduction pathway that utilizes a receptor tyrosine kinase and a Ras protein mediates the induction of vulval cell fates in the nematode Caenorhabditis elegans. We sought new genes that function in this pathway by screening for suppressors of the Multivulva phenotype caused by a mutation that activates the let-60 ras gene. Seven such suppressor mutations defined a new gene involved in vulval induction. We named this gene mek-2, because its predicted protein product is most similar to MEK, a protein-serine\/threonine and tyrosine kinase. mek-2 mutations can be arranged in an allelic series. A probable null mutation eliminated vulval induction, and the strongest mutations alter codons conserved in most or all protein kinases. Our genetic analysis showed that mek-2 functions downstream of let-60 ras and is required for ras-mediated signal transduction in vivo. The MEK-2 protein may interact with the products of the lin-45 raf and mpk-1 MAP kinase genes, which also mediate vulval induction.<\/jats:p>","DOI":"10.1101\/gad.9.6.756","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T21:15:46Z","timestamp":1181078146000},"page":"756-768","source":"Crossref","is-referenced-by-count":80,"title":["The Caenorhabditis elegans gene mek-2 is required for vulval induction and encodes a protein similar to the protein kinase MEK."],"prefix":"10.1101","volume":"9","author":[{"given":"K","family":"Kornfeld","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K L","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H R","family":"Horvitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"246","published-online":{"date-parts":[[1995,3,15]]},"reference":[{"key":"2021111418212874000_9.6.756.1","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(92)90131-U"},{"key":"2021111418212874000_9.6.756.2","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-1.","volume":"13","year":"1994","journal-title":"EMBO J."},{"key":"2021111418212874000_9.6.756.3","doi-asserted-by":"publisher","DOI":"10.1038\/348693a0"},{"key":"2021111418212874000_9.6.756.4","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":"2021111418212874000_9.6.756.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2216"},{"key":"2021111418212874000_9.6.756.6","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/genetics\/125.1.29","article-title":"fog-1, a regulatory gene required for specification of spermatogenesis in the germ line of Caenorhabditis elegans.","volume":"125","year":"1990","journal-title":"Genetics"},{"key":"2021111418212874000_9.6.756.7","doi-asserted-by":"publisher","DOI":"10.1038\/348503a0"},{"key":"2021111418212874000_9.6.756.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.16.5848"},{"key":"2021111418212874000_9.6.756.9","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/20031967725"},{"key":"2021111418212874000_9.6.756.10","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90362-X"},{"key":"2021111418212874000_9.6.756.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5695"},{"key":"2021111418212874000_9.6.756.12","doi-asserted-by":"publisher","DOI":"10.1038\/356340a0"},{"key":"2021111418212874000_9.6.756.13","doi-asserted-by":"publisher","DOI":"10.1101\/SQB.1992.057.01.041"},{"key":"2021111418212874000_9.6.756.14","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1093\/genetics\/137.4.987","article-title":"The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins.","volume":"137","year":"1994","journal-title":"Genetics"},{"key":"2021111418212874000_9.6.756.15","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(77)90059-6"},{"key":"2021111418212874000_9.6.756.16","doi-asserted-by":"publisher","DOI":"10.1038\/335184a0"},{"key":"2021111418212874000_9.6.756.17","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90133-3"},{"key":"2021111418212874000_9.6.756.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.1411546"},{"key":"2021111418212874000_9.6.756.19","doi-asserted-by":"crossref","first-page":"14553","DOI":"10.1016\/S0021-9258(18)82362-6","article-title":"The mitogen-activated protein kinase signal transduction pathway.","volume":"268","year":"1993","journal-title":"J. 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