{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:19:00Z","timestamp":1779344340783,"version":"3.51.4"},"reference-count":81,"publisher":"American Society for Cell Biology (ASCB)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2000,11]]},"abstract":"<jats:p>SLI-1, a Caenorhabditis elegans homologue of the proto-oncogene product c-Cbl, is a negative regulator of LET-23-mediated vulval differentiation. Lack of SLI-1 activity can compensate for decreased function of the LET-23 epidermal growth factor receptor, the SEM-5 adaptor, but not the LET-60 RAS, suggesting that SLI-1 acts before RAS activation. SLI-1 and c-Cbl comprise an N-terminal region (termed SLI-1:N\/Cbl-N, containing a four-helix bundle, an EF hand calcium-binding domain, and a divergent SH2 domain) followed by a RING finger domain and a proline-rich C-terminus. In a transgenic functional assay, the proline-rich C-terminal domain is not essential for sli-1(+) function. A protein lacking the SH2 and RING finger domains has no activity, but a chimeric protein with the SH2 and RING finger domains of SLI-1 replaced by the equivalent domains of c-Cbl has activity. The RING finger domain of c-Cbl has been shown recently to enhance ubiquitination of active RTKs by acting as an E3 ubiquitin\u2013protein ligase. We find that the RING finger domain of SLI-1 is partially dispensable. Further, we identify an inhibitory tyrosine of LET-23 requiring sli-1(+) for its effects: removal of this tyrosine closely mimics the loss ofsli-1 but not of another negative regulator,ark-1. Thus, we suggest that this inhibitory tyrosine mediates its effects through SLI-1, which in turn inhibits signaling upstream of LET-60 RAS in a manner not wholly dependent on the ubiquitin\u2013ligase domain.<\/jats:p>","DOI":"10.1091\/mbc.11.11.4019","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T23:43:02Z","timestamp":1372808582000},"page":"4019-4031","source":"Crossref","is-referenced-by-count":29,"title":["Requirements of Multiple Domains of SLI-1, a<i>Caenorhabditis elegans<\/i>Homologue of c-Cbl, and an Inhibitory Tyrosine in LET-23 in Regulating Vulval Differentiation"],"prefix":"10.1091","volume":"11","author":[{"given":"Charles H.","family":"Yoon","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, California 91125"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chieh","family":"Chang","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, California 91125"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil A.","family":"Hopper","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, California 91125"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni M.","family":"Lesa","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, California 91125"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul W.","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, California 91125"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/348693a0","volume":"348","author":"Aroian R.V.","year":"1990","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/genetics\/128.2.251","volume":"128","author":"Aroian R.V.","year":"1991","journal-title":"Genetics"},{"key":"B3","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/0092-8674(94)90271-2","volume":"23","author":"Aronheim A.","year":"1994","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/348503a0","volume":"348","author":"Beitel G.","year":"1990","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/28548","volume":"394","author":"Boriack-Sjodin P.A.","year":"1998","journal-title":"Nature"},{"key":"B6","first-page":"1561","volume":"11","author":"Bowtell D.D.","year":"1995","journal-title":"Oncogene"},{"key":"B7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","volume":"77","author":"Brenner S.","year":"1974","journal-title":"Genetics"},{"key":"B8","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1038\/sj.onc.1202174","volume":"17","author":"Campbell S.L.","year":"1998","journal-title":"Oncogene"},{"key":"B9","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0092-8674(91)90639-G","volume":"64","author":"Cantley L.C.","year":"1991","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1093\/emboj\/19.13.3283","volume":"19","author":"Chang C.","year":"2000","journal-title":"EMBO J."},{"key":"B11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0960-9822(99)80112-2","volume":"9","author":"Chang C.","year":"1999","journal-title":"Curr. 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