{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:39:52Z","timestamp":1779345592496,"version":"3.51.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1997,6,1]],"date-time":"1997-06-01T00:00:00Z","timestamp":865123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,6,1]]},"abstract":"<jats:p>The Caenorhabditis elegans let-60 gene encodes a Ras protein that mediates induction of the hermaphrodite vulva. To better understand how mutations constitutively activate Ras and cause unregulated cell division, we have characterized ga89, a temperature-sensitive, gain-of-function mutation in let-60 ras. At 25\u00b0, ga89 increases let-60 activity resulting in a multivulva phenotype. At 15\u00b0, ga89 decreases let-60 activity resulting in a vulvaless phenotype in let-60(ga89)\/Df animals. The ga89 mutation causes a leucine (L) to phenylalanine (F) substitution at amino acid 19, a residue conserved in all Ras proteins. We introduced the L19F change into human H-Ras protein and found that the in vitro GTPase activity of H-Ras became temperature-dependent. Genetic experiments suggest that LET-60(L19F) interacts with GAP and GNEF, since mutations that decrease GAP and GNEF activity affect the multivulva phenotype of let-60(ga89) animals. These results suggest that the L19F mutation primarily affects the intrinsic rate of GTP hydrolysis by Ras, and that this effect may be sufficient to account for the activated-Ras phenotype caused by let-60(ga89). Our results suggest that a mutation in a human ras gene analogous to ga89 might contribute to oncogenic transformation.<\/jats:p>","DOI":"10.1093\/genetics\/146.2.553","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T22:45:38Z","timestamp":1610577938000},"page":"553-565","source":"Crossref","is-referenced-by-count":52,"title":["Mechanism of Activation of the <i>Caenorhabditis elegans ras<\/i> Homologue <i>let-60<\/i> by a Novel, Temperature-Sensitive, Gain-of-Function Mutation"],"prefix":"10.1093","volume":"146","author":[{"given":"David M","family":"Eisenmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart K","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1997,6,1]]},"container-title":["Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/genetics\/article-pdf\/146\/2\/553\/35202619\/genetics0553.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/genetics\/article-pdf\/146\/2\/553\/35202619\/genetics0553.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T20:38:52Z","timestamp":1619123932000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/genetics\/article\/146\/2\/553\/6053996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,6,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1997,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/genetics\/146.2.553","relation":{},"ISSN":["1943-2631"],"issn-type":[{"value":"1943-2631","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1997,6,1]]},"published":{"date-parts":[[1997,6,1]]}}}