{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:58:47Z","timestamp":1790384327486,"version":"4.1.0"},"reference-count":59,"publisher":"Cold Spring Harbor Laboratory","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1997,10,15]]},"abstract":"<jats:p>During induction of the<jats:italic>Caenorhabditis elegans<\/jats:italic>hermaphrodite vulva, a signal from the anchor cell activates the LET-23 epidermal growth factor receptor (EGFR)\/LET-60 Ras\/MPK-1 MAP kinase signaling pathway in the vulval precursor cells. We have characterized two mechanisms that limit the extent of vulval induction. First, we found that<jats:italic>gap-1<\/jats:italic>may directly inhibit the LET-60 Ras signaling pathway. We identified the<jats:italic>gap-1<\/jats:italic>gene in a genetic screen for inhibitors of vulval induction.<jats:italic>gap-1<\/jats:italic>is predicted to encode a protein similar to GTPase-activating proteins that likely functions to inhibit the signaling activity of LET-60 Ras. A loss-of-function mutation in<jats:italic>gap-1<\/jats:italic>suppresses the vulvaless phenotype of mutations in the<jats:italic>let-60 ras<\/jats:italic>signaling pathway, but a<jats:italic>gap-1<\/jats:italic>single mutant does not exhibit excess vulval induction. Second, we found that<jats:italic>let-23 EGFR<\/jats:italic>prevents vulval induction in a cell-nonautonomous manner, in addition to its cell-autonomous role in activating the<jats:italic>let-60 ras\/mpk-1<\/jats:italic>signaling pathway. Using genetic mosaic analysis, we show that<jats:italic>let-23<\/jats:italic>activity in the vulval precursor cell closest to the anchor cell (P6.p) prevents induction of vulval precursor cells further away from the anchor cell (P3.p, P4.p, and P8.p). This result suggests that LET-23 in proximal vulval precursor cells might bind and sequester the inductive signal LIN-3 EGF, thereby preventing diffusion of the inductive signal to distal vulval precursor cells.<\/jats:p>","DOI":"10.1101\/gad.11.20.2715","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T22:15:26Z","timestamp":1203545726000},"page":"2715-2728","source":"Crossref","is-referenced-by-count":84,"title":["Inhibition of<i>Caenorhabditis elegans<\/i>vulval induction by<i>gap-1<\/i>and by<i>let-23<\/i>receptor tyrosine\u2009kinase"],"prefix":"10.1101","volume":"11","author":[{"given":"Alex","family":"Hajnal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles W.","family":"Whitfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart K.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1997,10,15]]},"reference":[{"key":"2021111418475548000_11.20.2715.1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1990.9999"},{"key":"2021111418475548000_11.20.2715.2","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","author":"Aroian","year":"1991","journal-title":"Genetics"},{"key":"2021111418475548000_11.20.2715.3","doi-asserted-by":"publisher","DOI":"10.1038\/348693a0"},{"key":"2021111418475548000_11.20.2715.4","first-page":"360","article-title":"Mutations in the Caenorhabditis elegans let-23 EGFR-like gene define elements important for cell-type specificity and function.","volume":"12","author":"Aroian","year":"1993","journal-title":"EMBO J."},{"key":"2021111418475548000_11.20.2715.5","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490410615"},{"key":"2021111418475548000_11.20.2715.6","doi-asserted-by":"publisher","DOI":"10.1038\/348503a0"},{"key":"2021111418475548000_11.20.2715.7","doi-asserted-by":"publisher","DOI":"10.1038\/366643a0"},{"key":"2021111418475548000_11.20.2715.8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.7.1.601"},{"key":"2021111418475548000_11.20.2715.9","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/20031967725"},{"key":"2021111418475548000_11.20.2715.10","doi-asserted-by":"publisher","DOI":"10.1038\/362152a0"},{"key":"2021111418475548000_11.20.2715.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81374-4"},{"key":"2021111418475548000_11.20.2715.12","doi-asserted-by":"publisher","DOI":"10.1038\/356340a0"},{"key":"2021111418475548000_11.20.2715.13","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","author":"Clark","year":"1994","journal-title":"Genetics"},{"key":"2021111418475548000_11.20.2715.14","doi-asserted-by":"publisher","DOI":"10.1126\/science.7678707"},{"key":"2021111418475548000_11.20.2715.15","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(85)90439-7"},{"key":"2021111418475548000_11.20.2715.16","doi-asserted-by":"crossref","unstructured":"Eisenmann, D. and S. 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