{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:18:01Z","timestamp":1791253081992,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,8,20]]},"abstract":"<jats:p>Signaling through the interleukin 2 receptor (IL-2R) involves phosphorylation of several proteins including Jak3, STAT5, and, in preactivated cells, STAT3. In the present study, we examined the functional status of the IL-2R-associated Jak\/STAT pathway in malignant T lymphocytes from advanced skin-based lymphomas: anaplastic large T-cell lymphoma (ALCL) and Sezary syndrome (SzS). Proliferation of three ALCL cell lines (PB-1, 2A, and 2B) was partially inhibited by rapamycin, a blocker of some of the signals mediated by IL-2R, but not by cyclosporin A, FK-506, and prednisone, which suppress signals mediated by the T-cell receptor. All the cell lines expressed on their surface the high-affinity IL-2R (alpha, beta, and gamma c chains). They showed basal, constitutive phosphorylation, and coassociation of Jak3, STAT5, and STAT3. Weak basal phosphorylation of IL-2R gamma c was also detected. In regard to SzS, peripheral blood mononuclear cells from 10 of 14 patients showed basal phosphorylation of Jak3, accompanied by phosphorylation of STAT5 in 9 patients, and STAT3 in 4 patients. However, in vitro overnight culture of SzS cells without exogenous cytokines resulted in markedly decreased Jak3 and STAT5 phosphorylation, which could be reversed by stimulation with IL-2. This indicates that the basal phosphorylation of Jak3 and STAT5 in freshly isolated SzS cells is induced rather than constitutive. The basal activation of the Jak\/STAT pathway involved in IL-2R signal transduction in ALCL and SzS cells reported here suggests that this pathway may play a role in the pathogenesis of cutaneous T-cell lymphomas, although the mechanism (induced versus constitutive) may vary between different lymphoma types.<\/jats:p>","DOI":"10.1073\/pnas.93.17.9148","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"9148-9153","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":201,"title":["Activation of Jak\/STAT proteins involved in signal transduction pathway mediated by receptor for interleukin 2 in malignant T lymphocytes derived from cutaneous anaplastic large T-cell lymphoma and Sezary syndrome."],"prefix":"10.1073","volume":"93","author":[{"given":"Q","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Pennsylvania Medical Center, Philadelphia 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania Medical Center, Philadelphia 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E C","family":"Vonderheid","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania Medical Center, Philadelphia 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A H","family":"Rook","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania Medical Center, Philadelphia 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M E","family":"Kadin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania Medical Center, Philadelphia 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P C","family":"Nowell","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania Medical Center, Philadelphia 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L M","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania Medical Center, Philadelphia 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Wasik","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania Medical Center, Philadelphia 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,8,20]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.17.9148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T15:17:04Z","timestamp":1649863024000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.17.9148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,8,20]]},"references-count":0,"journal-issue":{"issue":"17","published-print":{"date-parts":[[1996,8,20]]}},"alternative-id":["10.1073\/pnas.93.17.9148"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.17.9148","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,8,20]]},"assertion":[{"value":"1996-08-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}