Journal ArticleDOI
Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells
Bruce A. Witthuhn,Olli Silvennoinen,Osamu Miura,Osamu Miura,Koon Siew Lai,Christopher Cwik,Edison T. Liu,James N. Ihle +7 more
TLDR
A new Jak family kinase is described, and it is demonstrated that Jak-3, and to a lesser extent Jak-1, are tyrosine phosphorylated and Jak- 3 is activated in the responses to interleukin-2 and interLEukin–4 in T cells and myeloid cells.Abstract:
Many cytokines function through interaction with receptors of the cytokine receptor superfamily. Although lacking catalytic domains, cytokine receptors couple ligand binding to induction of protein tyrosine phosphorylation. Recent studies have shown that one or more of the Janus kinase family members (Jaks) associate with cytokine receptors and are tyrosine phosphorylated and activated following ligand binding. Here we describe a new Jak family kinase, Jak-3, and demonstrate that Jak-3, and to a lesser extent Jak-1, are tyrosine phosphorylated and Jak-3 is activated in the responses to interleukin-2 and interleukin-4 in T cells and myeloid cells. Jak-3 activation requires the serine-rich, membrane-proximal domain of the interleukin-2 receptor beta-chain, but does not require the acidic domain that is required for association and activation of Src family kinases.read more
Citations
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Journal ArticleDOI
JAKS AND STATS: Biological Implications*
Warren J. Leonard,John J. O'Shea +1 more
TL;DR: The Jak-STAT pathway is the focus of this chapter, a novel mechanism in which cytosolic latent transcription factors, known as signal transducers and activators of transcription (STATs), are tyrosine phosphorylated by Janus family tyrosin kinases (Jaks), allowing STAT protein dimerization and nuclear translocation.
Journal ArticleDOI
Stat6 Is Required for Mediating Responses to IL-4 and for the Development of Th2 Cells
TL;DR: It is demonstrated that, despite the existence of multiple signaling pathways activated by IL-4, Stat6 is essential for mediating responses toIL-4 lymphocytes.
Journal ArticleDOI
The IL-4 receptor: signaling mechanisms and biologic functions.
TL;DR: The modular nature of the IL-4 receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation are emphasized.
Journal ArticleDOI
The JAK-STAT pathway at twenty.
George R. Stark,James E. Darnell +1 more
TL;DR: This initial description of the JAK-STAT pathway led quickly to additional discoveries that type II interferons and many other cytokines signal through similar mechanisms, and it now serves as a paradigm showing how information from protein-protein contacts at the cell surface can be conveyed directly to genes in the nucleus.
Journal ArticleDOI
The ifn-gamma receptor: a paradigm for cytokine receptor signaling
TL;DR: A model of IFN gamma signaling that is nearly complete and that serves as a paradigm for signaling by other members of the cytokine receptor superfamily is produced.
References
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Journal ArticleDOI
JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin
Bruce A. Witthuhn,Frederick W. Quelle,Olli Silvennoinen,Taolin Yi,Bo Tang,Osamu Miura,James N. Ihle +6 more
TL;DR: The results support the hypothesis that JAK2 is the kinase that couples EPO binding to tyrosine phosphorylation and mitogenesis.
Journal ArticleDOI
The V(D)J Recombination Activating Gene, RAG-1
TL;DR: The RAG-1 (recombination activating gene-1) genomic locus, which activates V(D)J recombination when introduced into NIH 3T3 fibroblasts, was isolated by serial genomic transfections of oligonucleotide-tagged DNA.
Journal ArticleDOI
Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway
Shizuo Akira,Yukihiro Nishio,Masahiro Inoue,Xue-Jie Wang,Shi We,Taiji Matsusaka,Kanji Yoshida,Tetsuo Sudo,Masanobu Naruto,Tadamitsu Kishimoto +9 more
TL;DR: The purification and cloning of APRF are reported and it is observed that p91 is not tyrosine phosphorylated in response to IL-6, and that selective activation of p91-related factors may explain the diversity of cellular responses to different cytokines.