ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5

Smedley, Damian, Demiroglu, Asuman, Abdul-Rauf, Munah, Heath, Carol, Cooper, Colin ORCID: https://orcid.org/0000-0003-2013-8042, Shipley, Janet and Cross, Nicholas C. P. (1999) ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5. Neoplasia, 1 (4). pp. 349-355. ISSN 1522-8002

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The ZNF198-FGFR1 fusion gene arises as a result of the t(8;13)(p11;q12) in the 8p11 myeloproliferative syndrome. To determine the transforming properties of this chimeric protein we transfected ZNF198-FGFR1 into the interleukin (IL)-3 dependent cell line Ba/F3. Growth factor independent subclones were obtained in which ZNF198-FGFR1, STAT1, and STAT5 were constitutively tyrosine phosphorylated, as determined by immunoprecipitation and Western blot analysis. To test the hypothesis that constitutive activation of ZNF198-FGFR1 tyrosine kinase activity is a result of self-association of the fusion protein, we in vitro transcribed and translated ZNF198-FGFR1 and a derivative construct, ZNF198-FGFR1ΔC-myc, in which the C-terminal FGFR1 epitope was replaced by a c-myc tag. As expected, an anti-FGFR1 antibody immunoprecipitated ZNF198-FGFR1 but not ZNF198-FGFR1ΔC-myc. However when both products were translated together, both were coimmunoprecipitated by anti-FGFR1 antisera. Similar results were obtained by using an anti-myc antibody and demonstrated a physical interaction between the two proteins. Analysis of COS-7 cells transfected with ZNF198-FGFR1 demonstrated that the fusion gene, in contrast to normal FGFR1, is located in the cytoplasm. We conclude that ZNF198-FGFR1 is a cytoplasmic protein that self-associates and has constitutive transformation activity. These data suggest that ZNF198-FGFR1 plays a primary role in the pathogenesis of the t(8;13) myeloproliferative syndrome and Is the first report to implicate STAT proteins in FGFR1-mediated signaling.

Item Type: Article
Additional Information: Funding Information: This work was supported by the Kay Kendall Leukemia Fund, the Leukemia Research Fund, and The Medical Research Council.
Uncontrolled Keywords: fgfr1,t(8;13),tyrosine kinase,znf193,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1306
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
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Depositing User: LivePure Connector
Date Deposited: 18 Jul 2022 15:31
Last Modified: 23 Oct 2022 04:01
URI: https://ueaeprints.uea.ac.uk/id/eprint/86486
DOI: 10.1038/sj.neo.7900035

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