Jak-STAT signaling induced by the v-abl oncogene.

The effect of the v-abl oncogene of the Abelson murine leukemia virus (A-MuLV) on the Jak-STAT pathway of cytokine signal transduction was investigated. In murine pre-B lymphocytes transformed with A-MuLV, the Janus kinases (Jaks) Jak1 and Jak3 exhibited constitutive tyrosine kinase activity, and the STAT proteins (signal transducers and activators of transcription) normally activated by interleukin-4 and interleukin-7 were tyrosine-phosphorylated in the absence of these cytokines. Coimmunoprecipitation experiments revealed that in these cells v-Abl was physically associated with Jak1 and Jak3. Inactivation of v-Abl tyrosine kinase in a pre-B cell line transformed with a temperature-sensitive mutant of v-abl resulted in abrogation of constitutive Jak-STAT signaling. A direct link may exist between transformation by v-abl and cytokine signal transduction.

[1]  W. Leonard,et al.  Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I. , 1995, Science.

[2]  Sanjay Gupta,et al.  γ Chain-associated Cytokine Receptors Signal through Distinct Transducing Factors (*) , 1995, The Journal of Biological Chemistry.

[3]  S. McKnight,et al.  Identification and purification of human Stat proteins activated in response to interleukin-2. , 1995, Immunity.

[4]  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.

[5]  S. McKnight,et al.  An interleukin-4-induced transcription factor: IL-4 Stat. , 1994, Science.

[6]  D. Levy,et al.  Cytokines and growth factors signal through tyrosine phosphorylation of a family of related transcription factors. , 1994, Immunity.

[7]  J. Darnell,et al.  Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. , 1994, Science.

[8]  O. Silvennoinen,et al.  Signaling by the cytokine receptor superfamily: JAKs and STATs. , 1994, Trends in biochemical sciences.

[9]  D. Baltimore,et al.  Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase , 1994, Molecular and cellular biology.

[10]  N. Rosenberg,et al.  An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement. , 1994, Genes & development.

[11]  C. Schindler,et al.  STF‐IL‐4: a novel IL‐4‐induced signal transducing factor. , 1994, The EMBO journal.

[12]  O. Colamonici,et al.  p135tyk2, an interferon-alpha-activated tyrosine kinase, is physically associated with an interferon-alpha receptor. , 1994, The Journal of biological chemistry.

[13]  D. Levy,et al.  Interferon-induced nuclear signalling by Jak protein tyrosine kinases , 1993, Nature.

[14]  G. Stark,et al.  The protein tyrosine kinase JAK1 complements defects in interferon-α/β and -γ signal transduction , 1993, Nature.

[15]  C. Schindler,et al.  Early events in signalling by interferons. , 1993, Trends in biochemical sciences.

[16]  N. Rosenberg,et al.  Lymphoid cells transformed by Abelson virus require the v-abl protein-tyrosine kinase only during early G1. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  D. Baltimore,et al.  Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo , 1992, Molecular and cellular biology.

[18]  O. Witte,et al.  Hyperexpression of interleukin-7 is not necessary or sufficient for transformation of a pre-B lymphoid cell line , 1991, Molecular and cellular biology.

[19]  A. Engelman,et al.  Temperature-sensitive mutants of Abelson murine leukemia virus deficient in protein tyrosine kinase activity , 1990, Journal of virology.

[20]  A. Engelman,et al.  bcr/abl and src but not myc and ras replace v-abl in lymphoid transformation , 1990, Molecular and cellular biology.

[21]  J. Gimble,et al.  Cells and molecules that regulate B lymphopoiesis in bone marrow. , 1989, Annual review of immunology.

[22]  I. Weissman,et al.  Bone marrow stromal cell lines with lymphopoietic activity express high levels of a pre-B neoplasia-associated molecule , 1987, Cell.

[23]  O. Witte,et al.  A single bone marrow-derived stromal cell type supports the in vitro growth of early lymphoid and myeloid cells , 1987, Cell.

[24]  O. Witte,et al.  Activation of the abl oncogene in murine and human leukemias. , 1985, Biochimica et biophysica acta.

[25]  J. Pumphrey,et al.  Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanism , 1985, Cell.

[26]  A. Burgess,et al.  Malignant transformation of a growth factor-dependent myeloid cell line by Abelson virus without evidence of an autocrine mechanism , 1985, Cell.

[27]  D. Baltimore,et al.  The minimum transforming region of v-abl is the segment encoding protein-tyrosine kinase , 1985, Journal of virology.

[28]  S. Ziegler,et al.  Differentiation of cloned populations of immature B cells after transformation with abelson murine leukemia virus , 1983, Cell.

[29]  David Baltimore,et al.  Organization and reorganization of immunoglobulin genes in A-MuLV-transformed cells: Rearrangement of heavy but not light chain genes , 1981, Cell.

[30]  D. Baltimore,et al.  Structure of the abelson murine leukemia virus genome , 1979, Cell.