title: ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain.
abstract: An acquired chromosomal translocation, t(8;13)(p11;q11-12), observed in a distinctive type of stem cell leukemia/lymphoma syndrome, leads to the fusion of the 5' portion of ZNF198 and the 3' portion of FGFR1. ZNF198-FGFR1 fusion transcripts encode 4 to 10 zinc fingers, a proline-rich region, and the intracellular portion of the FGFR1 (fibroblast growth factor receptor 1) receptor tyrosine kinase. We demonstrate that the ZNF198 proline-rich region constitutes a novel self-association domain. When fused to the intracellular domain of FGFR1, the ZNF198 proline-rich region is sufficient to cause oligomerization, FGFR1 tyrosine kinase activation, and transformation of Ba/F3 cells to IL-3 independent growth. (Blood. 2000;96:699-704)
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, the Dana-Farber Cancer Institute, and the Division of Hematology-Oncology, Children's Hospital, Boston, MA.sxaio@rics.bwh.harvard.edu
authors.forename: S
authors.initials: S
authors.lastname: Xiao
authors.forename: J G
authors.initials: JG
authors.lastname: McCarthy
authors.forename: J C
authors.initials: JC
authors.lastname: Aster
authors.forename: J A
authors.initials: JA
authors.lastname: Fletcher
mesh_terms: D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006412:Hematopoietic Stem Cells; D016399:Lymphoma, T-Cell / Q000235:genetics; D046911:Macromolecular Substances; D051379:Mice; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011392:Proline; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C498438:Zmym2 protein, mouse; D019000:Phosphotyrosine; D011392:Proline; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1