Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits.

The interleukin-2 receptor (IL-2R) consists of three subunits: the IL-2R alpha, IL-2R beta, and IL-2R gamma chains, the last of which is also used in the receptors for IL-4, IL-7, and IL-9. Stimulation with IL-2 induces the tyrosine phosphorylation and activation of the Janus kinases Jak1 and Jak3. Jak1 and Jak3 were found to be selectively associated with the "serine-rich" region of IL-2R beta and the carboxyl-terminal region of IL-2R gamma, respectively. Both regions were necessary for IL-2 signaling. Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. Thus, activation of Jak1 and Jak3 may be a key event in IL-2 signaling.

[1]  T. Taniguchi,et al.  Evidence for a critical role for the cytoplasmic region of the interleukin 2 (IL-2) receptor gamma chain in IL-2, IL-4, and IL-7 signalling , 1994, Molecular and cellular biology.

[2]  N. Tanaka,et al.  Physical association of JAK1 and JAK2 tyrosine kinases with the interleukin 2 receptor beta and gamma chains. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[3]  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.

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

[5]  N. Copeland,et al.  Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation , 1994, Molecular and cellular biology.

[6]  T. Taniguchi,et al.  Signal transduction mediated by the reconstituted IL-2 receptor. Evidence for a cell type-specific function of IL-2 receptor beta-chain. , 1994, Journal of immunology.

[7]  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.

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

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

[10]  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.

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

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

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

[14]  J. Cleveland,et al.  Structure of the murine Jak2 protein-tyrosine kinase and its role in interleukin 3 signal transduction. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[15]  O. Silvennoinen,et al.  JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin , 1993, Cell.

[16]  G. Zurawski,et al.  Receptors for interleukin‐13 and interleukin‐4 are complex and share a novel component that functions in signal transduction. , 1993, The EMBO journal.

[17]  R. Perlmutter,et al.  Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

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

[19]  W. Leonard,et al.  Interleukin-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans , 1993, Cell.

[20]  R. Perlmutter,et al.  Association of p56lck with IL‐2 receptor beta chain is critical for the IL‐2‐induced activation of p56lck. , 1993, The EMBO journal.

[21]  T. Taniguchi,et al.  The IL-2 receptor complex: its structure, function, and target genes. , 1993, Annual review of immunology.

[22]  K. Yasukawa,et al.  Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. Hatakeyama,et al.  The integrity of the conserved ‘WS motif’ common to IL‐2 and other cytokine receptors is essential for ligand binding and signal transduction. , 1991, The EMBO journal.

[24]  S. Nagata,et al.  Functional domains of the granulocyte colony‐stimulating factor receptor. , 1991, The EMBO journal.

[25]  G. Mills,et al.  A tyrosine kinase physically associates with the beta-subunit of the human IL-2 receptor. , 1991, Journal of immunology.

[26]  R. Perlmutter,et al.  Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association , 1991, Science.

[27]  J. Bazan,et al.  Structural design and molecular evolution of a cytokine receptor superfamily. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[28]  C. March,et al.  A new cytokine receptor superfamily. , 1990, Trends in biochemical sciences.

[29]  T. Taniguchi,et al.  A restricted cytoplasmic region of IL-2 receptor β chain is essential for growth signal transduction but not for ligand binding and internalization , 1989, Cell.

[30]  D. Ferris,et al.  Two-dimensional analysis of interleukin 2-regulated tyrosine kinase activation mediated by the p70-75 beta subunit of the interleukin 2 receptor. , 1989, The Journal of biological chemistry.

[31]  T. Waldmann The multi-subunit interleukin-2 receptor. , 1989, Annual review of biochemistry.

[32]  Kendall A. Smith,et al.  Interleukin-2: inception, impact, and implications. , 1988, Science.