ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5
The ZNF198-FGFR1 fusion gene arises as a result of the t(8;13)(p11;g12) 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 we...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1999-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558699800268 |
| _version_ | 1811285822276632576 |
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| author | Damian Smedley Asuman Demiroglu Munah Abdul-Rauf Carol Heatht Colin Cooper Janet Shipley Nicholas C.P. Cross |
| author_facet | Damian Smedley Asuman Demiroglu Munah Abdul-Rauf Carol Heatht Colin Cooper Janet Shipley Nicholas C.P. Cross |
| author_sort | Damian Smedley |
| collection | DOAJ |
| description | The ZNF198-FGFR1 fusion gene arises as a result of the t(8;13)(p11;g12) 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, 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 selfassociation 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-FGFRi 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. |
| first_indexed | 2024-04-13T02:49:37Z |
| format | Article |
| id | doaj.art-8b2aa741b0584f9aa3b351e45cd8875e |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-13T02:49:37Z |
| publishDate | 1999-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-8b2aa741b0584f9aa3b351e45cd8875e2022-12-22T03:05:53ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80021999-10-011434935510.1038/sj.neo.7900035ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5Damian Smedley0Asuman Demiroglu1Munah Abdul-Rauf2Carol Heatht3Colin Cooper4Janet Shipley5Nicholas C.P. Cross6Molecular Carcinogenesis Section, Institute of Cancer Research, Haddow Laboratories, Belmont, Surrey, UKDepartment of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, UKMolecular Carcinogenesis Section, Institute of Cancer Research, Haddow Laboratories, Belmont, Surrey, UKMolecular Carcinogenesis Section, Institute of Cancer Research, Haddow Laboratories, Belmont, Surrey, UKMolecular Carcinogenesis Section, Institute of Cancer Research, Haddow Laboratories, Belmont, Surrey, UKMolecular Carcinogenesis Section, Institute of Cancer Research, Haddow Laboratories, Belmont, Surrey, UKDepartment of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, UKThe ZNF198-FGFR1 fusion gene arises as a result of the t(8;13)(p11;g12) 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, 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 selfassociation 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-FGFRi 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.http://www.sciencedirect.com/science/article/pii/S1476558699800268ZNF198FGFR1t(8;13)tyrosine kinase |
| spellingShingle | Damian Smedley Asuman Demiroglu Munah Abdul-Rauf Carol Heatht Colin Cooper Janet Shipley Nicholas C.P. Cross ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5 Neoplasia: An International Journal for Oncology Research ZNF198 FGFR1 t(8;13) tyrosine kinase |
| title | ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5 |
| title_full | ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5 |
| title_fullStr | ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5 |
| title_full_unstemmed | ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5 |
| title_short | ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5 |
| title_sort | znf198 fgfr1 transforms ba f3 cells to growth factor independence and results in high level tyrosine phosphorylation of stats 1 and 5 |
| topic | ZNF198 FGFR1 t(8;13) tyrosine kinase |
| url | http://www.sciencedirect.com/science/article/pii/S1476558699800268 |
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