Journal ArticleDOI
A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma
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TLDR
Interferon-gamma stimulates transcription of specific genes by inducing tyrosine phosphorylation of a 91-kilodalton cytoplasmic protein ( STAT for signal transducer and activator of transcription).Abstract:
Interferon-gamma (IFN-gamma) stimulates transcription of specific genes by inducing tyrosine phosphorylation of a 91-kilodalton cytoplasmic protein (termed STAT for signal transducer and activator of transcription). Stat91 was phosphorylated on a single site (Tyr701), and phosphorylation of this site was required for nuclear translocation, DNA binding, and gene activation. Stat84, a differentially spliced product of the same gene that lacks the 38 carboxyl-terminal amino acids of Stat91, did not activate transcription, although it was phosphorylated and translocated to the nucleus and bound DNA. Thus, Stat91 mediates activation of transcription in response to IFN-gamma.read more
Citations
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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).
Journal ArticleDOI
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
Protein modules and signalling networks
TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.
References
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Book ChapterDOI
Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates.
TL;DR: This chapter discusses the phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates, a powerful technique to help determine peptide structure and composition of proteins.
Journal ArticleDOI
Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor.
TL;DR: The interferon-alpha-stimulated gene factor 3 (ISGF3), a transcriptional activator, contains three proteins that reside in the cell cytoplasm until they are activated in response to IFN-alpha, and may link occupation of a specific polypeptide receptor with activation of transcription of a set of specific genes.
Journal ArticleDOI
Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein
TL;DR: Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha.
Journal ArticleDOI
Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha.
TL;DR: Several antibodies raised against these proteins prove that they indeed do encode protein components of ISGF-3, and provides reagents to explore the modification of this cytoplasmically activated transcription factor.
Journal Article
Optimized use of the firefly luciferase assay as a reporter gene in mammalian cell lines.
TL;DR: Several modifications of the luciferase assay are developed and certain parameters of the assay are characterized, resulting in optimization of conditions for the preparation and storage of cell lysates and establishment of substrate concentrations.