Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I.

Human T cell lymphotropic virus I (HTLV-I) is the etiological agent for adult T cell leukemia and tropical spastic paraparesis (also termed HTLV-I-associated myelopathy). HTLV-I-infected peripheral blood T cells exhibit an initial phase of interleukin-2 (IL-2)-dependent growth; over time, by an unknown mechanism, the cells become IL-2-independent. Whereas the Jak kinases Jak1 and Jak3 and the signal transducer and activator of transcription proteins Stat3 and Stat5 are activated in normal T cells in response to IL-2, this signaling pathway was constitutively activated in HTLV-I-transformed cells. In HTLV-I-infected cord blood lymphocytes, the transition from IL-2-dependent to IL-2-independent growth correlated with the acquisition of a constitutively activated Jak-STAT pathway, which suggests that this pathway participates in HTLV-I-mediated T cell transformation.

[1]  W. Leonard,et al.  The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15. , 1995, Immunity.

[2]  I. Kerr,et al.  Activation of JAK kinases and STAT proteins by interleukin‐2 and interferon alpha, but not the T cell antigen receptor, in human T lymphocytes. , 1994, The EMBO journal.

[3]  O. Silvennoinen,et al.  Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits. , 1994, Science.

[4]  J. Gribben,et al.  Prevention of T cell anergy by signaling through the gamma c chain of the IL-2 receptor. , 1994, Science.

[5]  J. Johnston,et al.  Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID. , 1994, Science.

[6]  E. Liu,et al.  Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells , 1994, Nature.

[7]  J. Johnston,et al.  Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2 , 1994, Nature.

[8]  J. Johnston,et al.  Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. Cosman,et al.  Utilization of the beta and gamma chains of the IL‐2 receptor by the novel cytokine IL‐15. , 1994, The EMBO journal.

[10]  B. Nelson,et al.  Cytoplasmic domains of the interleukin-2 receptor β and γ chains mediate the signal for T-cell proliferation , 1994, Nature.

[11]  M. Erdos,et al.  Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling , 1994, Nature.

[12]  T. Waldmann,et al.  A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[13]  T. Waldmann,et al.  The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[14]  W. Leonard,et al.  The Molecular Basis of X‐Linked Severe Combined Immunodeficiency: The Role of the Interleukin‐2 Receptor γ Chain as a Common γ Chain, γc , 1994, Immunological reviews.

[15]  S. Nishikawa,et al.  Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes. , 1994, Science.

[16]  S. Ziegler,et al.  Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. , 1993, Science.

[17]  K. Arai,et al.  Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. , 1993, Science.

[18]  R. Schlegel,et al.  The human T-cell leukemia/lymphotropic virus type I p12I protein cooperates with the E5 oncoprotein of bovine papillomavirus in cell transformation and binds the 16-kilodalton subunit of the vacuolar H+ ATPase , 1993, Journal of virology.

[19]  T. Taniguchi,et al.  The IL-2 IL-2 receptor system: A current overview , 1993, Cell.

[20]  I. Koralnik,et al.  The p12I, p13II, and p30II proteins encoded by human T-cell leukemia/lymphotropic virus type I open reading frames I and II are localized in three different cellular compartments , 1993, Journal of virology.

[21]  Z. Berneman,et al.  Protein isoforms encoded by the pX region of human T-cell leukemia/lymphotropic virus type I. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  N. Tanaka,et al.  Cloning of the gamma chain of the human IL-2 receptor. , 1992, Science.

[23]  J. Sodroski,et al.  Role of human T-cell leukemia virus type 1 X region proteins in immortalization of primary human lymphocytes in culture , 1992, Journal of virology.

[24]  D. Hafler,et al.  Characterization of HTLV-I in vivo infected T cell clones. IL-2-independent growth of nontransformed T cells. , 1992, Journal of immunology.

[25]  M. Reitz,et al.  Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[26]  G. Pavlakis,et al.  Complex splicing in the human T-cell leukemia virus (HTLV) family of retroviruses: novel mRNAs and proteins produced by HTLV type I , 1992, Journal of virology.

[27]  T. Ariga,et al.  Progress in primary immunodeficiency. , 1992, Immunology today.

[28]  R. de Waal Malefyt,et al.  Human T cell leukemia/lymphoma virus type I infection of a CD4+ proliferative/cytotoxic T cell clone progresses in at least two distinct phases based on changes in function and phenotype of the infected cells. , 1989, Journal of immunology.

[29]  M. Tsudo,et al.  Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[30]  M. Matsuoka,et al.  Evidence for the interleukin-2 dependent expansion of leukemic cells in adult T cell leukemia. , 1987, Blood.

[31]  M. Yoshida,et al.  Recent advances in the molecular biology of HTLV-1: trans-activation of viral and cellular genes. , 1987, Annual review of immunology.

[32]  R C Gallo,et al.  The first human retrovirus. , 1986, Scientific American.

[33]  S. Arya,et al.  T-cell growth factor gene: lack of expression in human T-cell leukemia-lymphoma virus-infected cells. , 1984, Science.

[34]  D. Mann,et al.  Transformation of human umbilical cord blood T cells by human T-cell leukemia/lymphoma virus. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[35]  M. Kannagi,et al.  Transformation of human leukocytes by cocultivation with an adult T cell leukemia virus producer cell line. , 1982, Science.

[36]  Y. Ohtsuki,et al.  Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells , 1981, Nature.