Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells
| Autor: | Shin-Heh Kang, Michael I. Nerenberg, Xiao Xu, John J. O'Shea, Olaf Heidenreich, M. Okerholm |
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| Rok vydání: | 1995 |
| Předmět: |
T-Lymphocytes
T cell Molecular Sequence Data T-cell leukemia Gene Expression Mice Transgenic Biology Transfection Polymerase Chain Reaction 3T3 cells Cell Line Mice chemistry.chemical_compound Proto-Oncogene Proteins Tumor Cells Cultured medicine Animals Humans DNA Primers Human T-lymphotropic virus 1 Base Sequence Interleukin-6 Kinase Janus kinase 3 NF-kappa B Janus Kinase 3 Tyrosine phosphorylation 3T3 Cells Gene Products tax Receptors Interleukin General Medicine Janus Kinase 2 Protein-Tyrosine Kinases Cell Transformation Viral Receptors Interleukin-6 Molecular biology Enzyme Activation Kinetics medicine.anatomical_structure chemistry Phosphorylation Oligonucleotide Probes Tyrosine kinase Cell Division Research Article |
| Zdroj: | Journal of Clinical Investigation. 96:1548-1555 |
| ISSN: | 0021-9738 |
| Popis: | HTLV-1 infection causes an adult T cell leukemia in humans. The viral encoded protein tax, is thought to play an important role in oncogenesis. Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes, despite comparable levels of tax expression in both tissues. Constitutive tyrosine phosphorylation of a 130-kD protein(s) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines, but not in thymocytes from Thy-tax transgenic mice. Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies, identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines. Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6. Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line, which was associated with induction of cell proliferation. Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies. Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model. |
| Databáze: | OpenAIRE |
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