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 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.
Xu
X
X
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
Kang
S H
SH
Heidenreich
O
O
Okerholm
M
M
O'Shea
J J
JJ
Nerenberg
M I
MI
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002472:Cell Transformation, Viral; D017931:DNA Primers; D004789:Enzyme Activation; D015870:Gene Expression; D016356:Gene Products, tax / Q000096:biosynthesis*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin / Q000096:biosynthesis; D019947:Receptors, Interleukin-6; D013601:T-Lymphocytes; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016356:Gene Products, tax; D015850:Interleukin-6; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507933:JAK3 protein, human; C507926:Jak2 protein, mouse; C507935:Jak3 protein, mouse; D053614:Janus Kinase 2; D053616:Janus Kinase 3