{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:29:15Z","timestamp":1791340155616,"version":"4.3.1"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,12,27]]},"abstract":"<jats:p>\n                    A recurrent somatic activating mutation in the nonreceptor tyrosine kinase\n                    <jats:italic>JAK2<\/jats:italic>\n                    (\n                    <jats:italic>JAK2V617F<\/jats:italic>\n                    ) occurs in the majority of patients with the myeloproliferative disorders polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, and, less commonly, chronic myelomonocytic leukemia. We do not understand the basis for the specificity of the\n                    <jats:italic>JAK2V617F<\/jats:italic>\n                    mutation in clonal disorders of the myeloid, but not lymphoid, lineage, nor has the basis for the pleiotropic phenotype of JAK2V617F-associated myeloproliferative disorders been delineated. However, the presence of the identical mutation in patients with related, but clinicopathologically distinct, myeloid disorders suggests that interactions between the JAK2V617F kinase and other signaling molecules may influence the phenotype of hematopoietic progenitors expressing JAK2V617F. Here, we show that coexpression of the JAK2V617F mutant kinase with a homodimeric Type I cytokine receptor, the erythropoietin receptor (EpoR), the thrombopoietin receptor, or the granulocyte colony-stimulating-factor receptor, is necessary for transformation of hematopoietic cells to growth-factor independence and for hormone-independent activation of JAK-STAT signaling. Furthermore, EpoR mutations that impair erythropoietin-mediated JAK2 or STAT5 activation also impair transformation mediated by the JAK2V617F kinase, indicating that JAK2V617F requires a cytokine receptor scaffold for its transforming and signaling activities. Our results reveal the molecular basis for the prevalence of JAK2V617F in diseases of myeloid lineage cells that express these Type I cytokine receptors but not in lymphoid lineage cells that do not.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0509714102","type":"journal-article","created":{"date-parts":[[2005,12,19]],"date-time":"2005-12-19T20:43:55Z","timestamp":1135025035000},"page":"18962-18967","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":278,"title":["Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation"],"prefix":"10.1073","volume":"102","author":[{"given":"Xiaohui","family":"Lu","sequence":"first","affiliation":[{"name":"Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142; and Division of Hematology, Department of Medicine, and Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Levine","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142; and Division of Hematology, Department of Medicine, and Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Tong","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142; and Division of Hematology, Department of Medicine, and Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerlinde","family":"Wernig","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142; and Division of Hematology, Department of Medicine, and Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Pikman","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142; and Division of Hematology, Department of Medicine, and Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Zarnegar","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142; and Division of Hematology, Department of Medicine, and Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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