{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:37:04Z","timestamp":1790671024553,"version":"4.1.0"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,5,23]]},"abstract":"<jats:p>\n                    Genetic abnormalities that result in expression of chimeric tyrosine kinase proteins such as BCR-ABL1 and ETV6-PDGFR\u03b2 are common causes of hematopoietic malignancies. The paradigm for constitutive activation of these fusion tyrosine kinases is enforced homodimerization by self-association domains present in the fusion partner proteins. The unique interstitial deletion on chromosome 4q12 that leads to expression of the FIP1L1-PDGFR\u03b1 fusion tyrosine kinase was recently identified as a cause of chronic eosinophilic leukemia. In this report, we demonstrate that FIP1L1 is completely dispensable for PDGFR\u03b1 activation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Instead, truncation of PDGFR\u03b1 between two conserved tryptophan residues in the juxtamembrane (JM) domain is required for kinase activation and transforming potential of FIP1L1-PDGFR\u03b1. The presence of a complete JM domain in FIP1L1-PDGFR\u03b1 is inhibitory, but this autoinhibition can be overcome by enforced homodimerization. Similar effects of the JM domain in the context of PDGFR\u03b2 were observed. These results suggest that disruption of the autoinhibitory JM domain is an alternative, dimerization-independent mechanism by which chimeric tyrosine kinases are constitutively activated and induce leukemogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0601192103","type":"journal-article","created":{"date-parts":[[2006,5,12]],"date-time":"2006-05-12T03:56:21Z","timestamp":1147406181000},"page":"8078-8083","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":109,"title":["Activation of FIP1L1-PDGFR\u03b1 requires disruption of the juxtamembrane domain of PDGFR\u03b1 and is FIP1L1-independent"],"prefix":"10.1073","volume":"103","author":[{"given":"Elizabeth H.","family":"Stover","sequence":"first","affiliation":[{"name":"*Division of Hematology, Department of Medicine, and"},{"name":"Department of Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Folens","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, 3000 Leuven, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin H.","family":"Lee","sequence":"additional","affiliation":[{"name":"*Division of Hematology, Department of Medicine, and"},{"name":"Department of Pathology, Brigham and Women's Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Mentens","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, 3000 Leuven, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Marynen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, 3000 Leuven, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ifor R.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pathology, Emory University, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Gary","family":"Gilliland","sequence":"additional","affiliation":[{"name":"*Division of Hematology, Department of Medicine, and"},{"name":"Department of Genetics, and"},{"name":"**Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Cools","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, 3000 Leuven, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,5,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra044389"},{"key":"e_1_3_3_2_2","first-page":"949","volume":"90","author":"Chalandon Y.","year":"2005","unstructured":"Y. Chalandon, J. 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