{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:56:05Z","timestamp":1779342965674,"version":"3.51.4"},"reference-count":0,"publisher":"American Society for Cell Biology (ASCB)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[1997,5]]},"abstract":"<jats:p> The major determinants of receptor tissue tyrosine kinase (RTK) signaling specificity have been proposed to be Src homology 2 (SH2) binding sites, phosphotyrosine-containing oligopeptides in the cytoplasmic domain of the receptor. The Caenorhabditis elegans epidermal growth factor receptor homologue LET-23 has multiple functions during development and has eight potential SH2-binding sites in a region carboxyl terminal to its kinase domain. By analyzing transgenic nematodes for three distinct LET-23 functions, we show that six of eight potential sites function in vivo and that they are required for most, but not all, of LET-23 activity. A single site is necessary and sufficient to promote wild-type fertility. Three other sites activate the RAS pathway and are involved only in viability and vulval differentiation. A fifth site is promiscuous and can mediate all three LET-23 functions. An additional site mediates tissue-specific negative regulation. Putative SH2 binding sites are thus key effectors of both cell-specific and negative regulation in an intact organism. We suggest two distinct mechanisms for tissue-specific RTK-mediated signaling. A positive mechanism would promote RTK function through effectors present only in certain cell types. A negative mechanism would inhibit RTK function through tissue-specific negative regulators. <\/jats:p>","DOI":"10.1091\/mbc.8.5.779","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T19:20:22Z","timestamp":1376680822000},"page":"779-793","source":"Crossref","is-referenced-by-count":34,"title":["Positive and negative tissue-specific signaling by a nematode epidermal growth factor receptor."],"prefix":"10.1091","volume":"8","author":[{"given":"G M","family":"Lesa","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, California Institute of Technology, Pasadena, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P W","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, California Institute of Technology, Pasadena, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1076","container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2019,7,14]],"date-time":"2019-07-14T09:16:47Z","timestamp":1563095807000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.8.5.779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,5]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1997,5]]}},"alternative-id":["10.1091\/mbc.8.5.779"],"URL":"https:\/\/doi.org\/10.1091\/mbc.8.5.779","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,5]]}}}