{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T22:35:19Z","timestamp":1791758119229,"version":"4.3.4"},"reference-count":48,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,7,16]]},"abstract":"<jats:p>The receptor subunit gp130 transduces multiple cell type\u2013specific activities of the leukemia inhibitory factor (LIF)\/interleukin (IL)-6 family of cytokines through the signal transducer and activator of transcription (STAT) and src homology 2 domain\u2013bearing protein tyrosine phosphatase (SHP)-2\/ras\/Erk pathways. To define STAT-dependent physiological responses, we generated mice with a COOH-terminal gp130\u0394STAT \u201cknock-in\u201d mutation which deleted all STAT-binding sites. gp130\u0394STAT mice phenocopyed mice deficient for IL-6 (impaired humoral and mucosal immune and hepatic acute phase responses) and LIF (failure of blastocyst implantation). However, unlike mice with null mutations in any of the components in the gp130 signaling pathway, gp130\u0394STAT mice also displayed gastrointestinal ulceration and a severe joint disease with features of chronic synovitis, cartilaginous metaplasia, and degradation of the articular cartilage. Mitogenic hyperresponsiveness of synovial cells to the LIF\/IL-6 family of cyto-kines was caused by sustained gp130-mediated SHP-2\/ras\/Erk activation due to impaired STAT-mediated induction of suppressor of cytokine signaling (SOCS) proteins which normally limits gp130 signaling. Therefore, the joint pathology in gp130\u0394STAT mice is likely to arise from the disturbance of the otherwise balanced activation of the SHP-2\/ras\/Erk and STAT signaling cascades emanating from gp130.<\/jats:p>","DOI":"10.1084\/jem.194.2.189","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"189-204","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":192,"title":["Defective Gp130-Mediated Signal Transducer and Activator of Transcription (Stat) Signaling Results in Degenerative Joint Disease, Gastrointestinal Ulceration, and Failure of Uterine Implantation"],"prefix":"10.1084","volume":"194","author":[{"given":"Matthias","family":"Ernst","sequence":"first","affiliation":[{"name":"aLudwig Institute for Cancer Research, PO Royal Melbourne Hospital, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Inglese","sequence":"additional","affiliation":[{"name":"aLudwig Institute for Cancer Research, PO Royal Melbourne Hospital, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Waring","sequence":"additional","affiliation":[{"name":"cDepartment of Pathology, Peter MacCallum Institute, East Melbourne VIC 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian K.","family":"Campbell","sequence":"additional","affiliation":[{"name":"bThe Walter and Eliza Hall Institute, PO Royal Melbourne Hospital, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisan","family":"Bao","sequence":"additional","affiliation":[{"name":"dDepartment of Pathology, University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona J.","family":"Clay","sequence":"additional","affiliation":[{"name":"aLudwig Institute for Cancer Research, PO Royal Melbourne Hospital, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren S.","family":"Alexander","sequence":"additional","affiliation":[{"name":"bThe Walter and Eliza Hall Institute, PO Royal Melbourne Hospital, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian P.","family":"Wicks","sequence":"additional","affiliation":[{"name":"bThe Walter and Eliza Hall Institute, PO Royal Melbourne Hospital, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Tarlinton","sequence":"additional","affiliation":[{"name":"bThe Walter and Eliza Hall Institute, PO Royal Melbourne Hospital, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Novak","sequence":"additional","affiliation":[{"name":"eDepartment of Surgery, The University of Melbourne Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan K.","family":"Heath","sequence":"additional","affiliation":[{"name":"aLudwig Institute for Cancer Research, PO Royal Melbourne Hospital, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley R.","family":"Dunn","sequence":"additional","affiliation":[{"name":"aLudwig Institute for Cancer Research, PO Royal Melbourne Hospital, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,7,16]]},"reference":[{"key":"2023072509513931200_R1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/bj3340297","article-title":"Interleukin-6-type cytokine signaling through the gp130\/Jak\/STAT pathway","volume":"334","author":"Heinrich","year":"1998","journal-title":"Biochem. 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