{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T21:55:07Z","timestamp":1770501307197,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,12,10]],"date-time":"2003-12-10T00:00:00Z","timestamp":1071014400000},"content-version":"vor","delay-in-days":2110,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[1998,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The Ras signalling pathway plays several important roles in the development of the nematode <jats:italic>Caenorhabditis elegans<\/jats:italic>. So far, two types of Ras\u2010GTPase activating proteins (Ras\u2010GAPs) have been identified in this organism. To aid the study of the regulation and function of the Ras pathway, we set out to isolate a new GAP gene from <jats:italic>C. elegans<\/jats:italic> by transcomplementation of the fission yeast <jats:italic>gap1<\/jats:italic> mutant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We isolated a <jats:italic>C. elegans<\/jats:italic> cDNA that encoded a protein which was similar to, but not exactly homologous with mammalian p120 Ras\u2010GAP. This gene, named <jats:italic>gap\u20102<\/jats:italic>, generated at least nine distinct mRNA species through transcription from different promoters and subsequent alternative splicing involving 25 exons. These isoforms were differentially expressed among tissues. A deletion of <jats:italic>gap\u20102<\/jats:italic> caused no obvious phenotype by itself, but a loss of <jats:italic>gap\u20102<\/jats:italic> function could suppress larval lethality in both <jats:italic>let\u201023<\/jats:italic> and <jats:italic>let\u201060<\/jats:italic> reduction\u2010of\u2010function mutants, in which the Ras activity was lowered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p> <jats:italic>C. elegans gap\u20102<\/jats:italic> encodes a novel Ras\u2010GAP, which is similar to vertebrate p120 but which may constitute a new GAP subfamily. <jats:italic>gap\u20102<\/jats:italic> mRNA isoforms arise by an unusually extensive variation in initiation sites and associated alternative splicing, and each isoform may play a distinct role in specific tissues. GAP\u20102 appears to function as a negative regulator of LET\u201060 Ras during larval development.<\/jats:p><\/jats:sec>","DOI":"10.1046\/j.1365-2443.1998.00179.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T22:39:37Z","timestamp":1047422377000},"page":"189-202","source":"Crossref","is-referenced-by-count":23,"title":["Characterization of the <i>C. elegans gap\u20102<\/i> gene encoding a novel Ras\u2010GTPase activating protein and its possible role in larval development"],"prefix":"10.1111","volume":"3","author":[{"given":"Seiji","family":"Hayashizaki","sequence":"first","affiliation":[]},{"given":"Yuichi","family":"Iino","sequence":"additional","affiliation":[]},{"given":"Masayuki","family":"Yamamoto","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2003,12,10]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/genetics\/128.2.251","article-title":"Multiple function of let\u201023, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction","volume":"128","author":"Aroian R.V.","year":"1991","journal-title":"Genetics"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.19.5227"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.56.070187.004023"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/348503a0"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/366643a0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/36849"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/77.1.71"},{"key":"e_1_2_6_9_2","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0021-9258(17)42184-3","article-title":"Characterization of a promiscuous GTPase\u2010activating protein that has a Bcr\u2010related domain from Caenorhabditis elegans","volume":"269","author":"Chen W.","year":"1994","journal-title":"J. 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