{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:56:56Z","timestamp":1791053816816,"version":"4.1.0"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,6,24]]},"abstract":"<jats:p>\n                    Mycosis fungoides (MF) is a low-grade cutaneous T cell lymphoma of unknown etiology. In this report, the Jak\/Stat (Janus kinase\/signal transducer and activator of transcription) signaling pathway was investigated in tumor cell lines established from skin biopsy specimens from a patient with MF. Jaks link cytokine receptors to Stats, and abnormal Jak\/Stat signaling has been observed in some hemopoietic cancers. In MF tumor cells, a slowly migrating isoform of Stat3, Stat3\n                    <jats:sup>sm<\/jats:sup>\n                    , was found to be constitutively activated, i.e., (\n                    <jats:italic>i<\/jats:italic>\n                    ) Stat3\n                    <jats:sup>sm<\/jats:sup>\n                    was constitutively phosphorylated on tyrosine residues, and tyrosine phosphorylation was not enhanced by growth factor stimulation; (\n                    <jats:italic>ii<\/jats:italic>\n                    ) band shift assays and immunoprecipitations of DNA\/Stat complexes showed constitutive DNA-binding properties of Stat3\n                    <jats:sup>sm<\/jats:sup>\n                    ; and (\n                    <jats:italic>iii<\/jats:italic>\n                    ) Stat3\n                    <jats:sup>sm<\/jats:sup>\n                    was constitutively associated with Jak3. The abnormal activation of Stat3\n                    <jats:sup>sm<\/jats:sup>\n                    was highly specific. Thus, neither the fast migrating isoform of Stat3 (Stat3\n                    <jats:sup>fm<\/jats:sup>\n                    ) nor other Stats (Stat1, Stat2, and Stat4 through Stat6) were constitutively activated. The Jak kinase inhibitor, tyrphostin AG490, blocked the constitutive activation of Stat3\n                    <jats:sup>sm<\/jats:sup>\n                    and inhibited spontaneous as well as interleukin 2-induced growth of MF tumor cells. In conclusion, we have provided evidence for an abnormal Jak\/Stat signaling and growth regulation in tumor cells obtained from affected skin of an MF patient.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.13.6764","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"6764-6769","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":195,"title":["Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: Tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor\u2009cell\u2009lines"],"prefix":"10.1073","volume":"94","author":[{"given":"Mette","family":"Nielsen","sequence":"first","affiliation":[{"name":"Institutes of Medical Microbiology and Immunology, and Medical Anatomy, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, 8000 C Aarhus, Denmark; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Institute for Cancer Studies, Sheffield University Medical School, Sheffield 2RX, England; and Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keld","family":"Kaltoft","sequence":"additional","affiliation":[{"name":"Institutes of Medical Microbiology and Immunology, and Medical Anatomy, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, 8000 C Aarhus, Denmark; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Institute for Cancer Studies, Sheffield University Medical School, Sheffield 2RX, England; and Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Nordahl","sequence":"additional","affiliation":[{"name":"Institutes of Medical Microbiology and Immunology, and Medical Anatomy, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, 8000 C Aarhus, Denmark; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Institute for Cancer Studies, Sheffield University Medical School, Sheffield 2RX, England; and Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"R\u00f6pke","sequence":"additional","affiliation":[{"name":"Institutes of Medical Microbiology and Immunology, and Medical Anatomy, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, 8000 C Aarhus, Denmark; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Institute for Cancer Studies, Sheffield University Medical School, Sheffield 2RX, England; and Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Geisler","sequence":"additional","affiliation":[{"name":"Institutes of Medical Microbiology and Immunology, and Medical Anatomy, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, 8000 C Aarhus, Denmark; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Institute for Cancer Studies, Sheffield University Medical School, Sheffield 2RX, England; and Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Mustelin","sequence":"additional","affiliation":[{"name":"Institutes of Medical Microbiology and Immunology, and Medical Anatomy, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, 8000 C Aarhus, Denmark; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Institute for Cancer Studies, Sheffield University Medical School, Sheffield 2RX, England; and Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Dobson","sequence":"additional","affiliation":[{"name":"Institutes of Medical Microbiology and Immunology, and Medical Anatomy, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, 8000 C Aarhus, Denmark; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Institute for Cancer Studies, Sheffield University Medical School, Sheffield 2RX, England; and Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Svejgaard","sequence":"additional","affiliation":[{"name":"Institutes of Medical Microbiology and Immunology, and Medical Anatomy, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, 8000 C Aarhus, Denmark; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Institute for Cancer Studies, Sheffield University Medical School, Sheffield 2RX, England; and Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"\u00d8dum","sequence":"additional","affiliation":[{"name":"Institutes of Medical Microbiology and Immunology, and Medical Anatomy, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, 8000 C Aarhus, Denmark; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Institute for Cancer Studies, Sheffield University Medical School, Sheffield 2RX, England; and Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital ..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,6,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1996.03890290088012"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8635(18)30176-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02631086"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.5.1973"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.5.1581"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12363017"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12363010"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0962-8924(96)10028-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07100.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7604283"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7541555"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7569929"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.3.811"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.5.1692.1692"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.17.9148"},{"key":"e_1_3_3_16_2","first-page":"23","volume":"11","author":"Nielsen M","year":"1994","unstructured":"M Nielsen, N Odum, K Bendtzen, L P Ryder, B K Jakobsen, A Svejgaard Exp Clin Immunogenet 11, 23\u201332 (1994).","journal-title":"Exp Clin Immunogenet"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830241225"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb07898.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.10.6201-6210.1993"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.22.13221"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.24.10995"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/379645a0"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.9.8756581"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.94.13.6764","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:48:18Z","timestamp":1649861298000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.94.13.6764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,6,24]]},"references-count":23,"journal-issue":{"issue":"13","published-print":{"date-parts":[[1997,6,24]]}},"alternative-id":["10.1073\/pnas.94.13.6764"],"URL":"https:\/\/doi.org\/10.1073\/pnas.94.13.6764","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,6,24]]},"assertion":[{"value":"1996-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1997-04-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1997-06-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}