Journal ArticleDOI
Contribution of STAT SH2 groups to specific interferon signaling by the Jak-STAT pathway
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TLDR
In response to specific ligands, various STAT proteins (signal transducers and activators of transcription) are phosphorylated on tyrosine by Jak protein kinases and translocated to the nucleus to direct gene transcription.Abstract:
In response to specific ligands, various STAT proteins (signal transducers and activators of transcription) are phosphorylated on tyrosine by Jak protein kinases and translocated to the nucleus to direct gene transcription. Selection of a STAT at the interferon gamma receptor as well as specific STAT dimer formation depended on the presence of particular SH2 groups (phosphotyrosine-binding domains), whereas the amino acid sequence surrounding the phosphorylated tyrosine on the STAT could vary. Thus, SH2 groups in STAT proteins may play crucial roles in specificity at the receptor kinase complex and in subsequent dimerization, whereas the kinases are relatively nonspecific.read more
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How cells respond to interferons
TL;DR: The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interFERons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
Journal ArticleDOI
Interferon-γ: an overview of signals, mechanisms and functions
TL;DR: The current understanding of IFN‐γ ligand, receptor, ignal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophages function during infection are reviewed.
Journal ArticleDOI
Principles of interleukin (IL)-6-type cytokine signalling and its regulation.
Peter C. Heinrich,Iris Behrmann,Serge Haan,Heike M. Hermanns,Gerhard Müller-Newen,Fred Schaper +5 more
TL;DR: This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction, with emphasis on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins.
Journal ArticleDOI
Cellular responses to interferon-gamma.
TL;DR: Much of the cellular response to IFN-gamma can be described in terms of a set of integrated molecular programs underlying well-defined physiological systems, for example the induction of efficient antigen processing for MHC-mediated antigen presentation, which play clearly defined roles in pathogen resistance.
Journal ArticleDOI
Interferon-Stimulated Genes: A Complex Web of Host Defenses
TL;DR: This review begins by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production and describes ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the Jak-STAT pathway.
References
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Journal ArticleDOI
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
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Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6
TL;DR: A new family member, Stat3, becomes activated through phosphorylation on tyrosine as a DNA binding protein in response to epidermal growth factor and interleukin-6 but not interferon gamma (IFN-gamma).
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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.
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A Short Polypeptide Marker Sequence Useful for Recombinant Protein Identification and Purification.
Thomas P. Hopp,K S Prickett,Virginia L. Price,Randell T. Libby,Carl J. March,Douglas P. Cerretti,David L. Urdal,Paul J. Conlon +7 more
TL;DR: A small hydrophilic peptide of eight amino acids was engineered onto the N-terminus of a variety of recombinant lymphokines for the purpose of aiding in their detection and purification from yeast supernatants or E. coli extracts.
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Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors
Neil Stahl,Thomas Farruggella,Teri G. Boulton,Zhong Zhong,James E. Darnell,George D. Yancopoulos +5 more
TL;DR: Selecting particular substrates that characterize responses to the ciliary neurotrophic factor-interleukin-6 cytokine family depended not on which Jak was activated, but was instead determined by specific tyrosine-based motifs in the receptor components--gp130 and LIFR--shared by these cytokines.