{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T15:21:46Z","timestamp":1769008906972,"version":"3.49.0"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T00:00:00Z","timestamp":1537920000000},"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":[[2018,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Investigation into the signaling relationship between closely related small GTPases Ras and Rap1 has a complicated past. Rasmussen, Dickinson, and Reiner use Caenorhabditis elegans to investigate the role of RAP-1 in LET-60\/ Ras-dependent developmental events...<\/jats:p>\n               <jats:p>The notoriety of the small GTPase Ras as the most mutated oncoprotein has led to a well-characterized signaling network largely conserved across metazoans. Yet the role of its close relative Rap1 (Ras Proximal), which shares 100% identity between their core effector binding sequences, remains unclear. A long-standing controversy in the field is whether Rap1 also functions to activate the canonical Ras effector, the S\/T kinase Raf. We used the developmentally simpler Caenorhabditis elegans, which lacks the extensive paralog redundancy of vertebrates, to examine the role of RAP-1 in two distinct LET-60\/Ras-dependent cell fate patterning events: induction of 1\u00b0 vulval precursor cell (VPC) fate and of the excretory duct cell. Fluorescence-tagged endogenous RAP-1 is localized to plasma membranes and is expressed ubiquitously, with even expression levels across the VPCs. RAP-1 and its activating GEF PXF-1 function cell autonomously and are necessary for maximal induction of 1\u00b0 VPCs. Critically, mutationally activated endogenous RAP-1 is sufficient both to induce ectopic 1\u00b0s and duplicate excretory duct cells. Like endogenous RAP-1, before induction GFP expression from the pxf-1 promoter is uniform across VPCs. However, unlike endogenous RAP-1, after induction GFP expression is increased in presumptive 1\u00b0s and decreased in presumptive 2\u00b0s. We conclude that RAP-1 is a positive regulator that promotes Ras-dependent inductive fate decisions. We hypothesize that PXF-1 activation of RAP-1 serves as a minor parallel input into the major LET-60\/Ras signal through LIN-45\/Raf.<\/jats:p>","DOI":"10.1534\/genetics.118.301601","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T22:05:12Z","timestamp":1537999512000},"page":"1339-1354","source":"Crossref","is-referenced-by-count":18,"title":["Ras-Dependent Cell Fate Decisions Are Reinforced by the RAP-1 Small GTPase in <i>Caenorhabditis<\/i> \u00a0<i>elegans<\/i>"],"prefix":"10.1093","volume":"210","author":[{"given":"Neal R","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Institute of Biosciences and Technology , College of Medicine, Texas A&M University, Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences , University of Texas, Austin, Texas 78705"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J","family":"Reiner","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Technology , College of Medicine, Texas A&M University, Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,9,26]]},"reference":[{"key":"2023042004150967700_bib1","doi-asserted-by":"publisher","first-page":"3545","DOI":"10.1242\/dev.068148","article-title":"Notch and Ras promote sequential steps of excretory tube development in C. elegans.","volume":"138","author":"Abdus-Saboor","year":"2011","journal-title":"Development"},{"key":"2023042004150967700_bib2","doi-asserted-by":"publisher","first-page":"7475","DOI":"10.1073\/pnas.95.13.7475","article-title":"Mitogenic and oncogenic properties of the small G protein Rap1b.","volume":"95","author":"Altschuler","year":"1998","journal-title":"Proc. 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