Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells

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...

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Bibliographic Details
Published in:	The Journal of clinical investigation Vol. 96; no. 3; pp. 1548 - 1555
Main Authors:	Xu, X, Kang, S H, Heidenreich, O, Okerholm, M, O'Shea, J J, Nerenberg, M I
Format:	Journal Article
Language:	English
Published:	United States 01-09-1995
Subjects:	3T3 Cells AIDS/HIV Animals Base Sequence Cell Division - drug effects Cell Line Cell Transformation, Viral DNA Primers Enzyme Activation Gene Expression Gene Products, tax - biosynthesis Human T-lymphotropic virus 1 - genetics Human T-lymphotropic virus 1 - metabolism Humans Interleukin-6 - biosynthesis Interleukin-6 - pharmacology Janus Kinase 2 Janus Kinase 3 Kinetics Mice Mice, Transgenic Molecular Sequence Data NF-kappa B - metabolism Oligonucleotide Probes Polymerase Chain Reaction Protein-Tyrosine Kinases - metabolism Proto-Oncogene Proteins Receptors, Interleukin - biosynthesis Receptors, Interleukin-6 T-Lymphocytes Transfection Tumor Cells, Cultured
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9738
DOI:	10.1172/JCI118193