Journal ArticleDOI
STATs and Gene Regulation
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TLDR
The discovery of a STAT in Drosophila, and most recently in Dictyostelium discoideum, implies an ancient evolutionary origin for this dual-function set of proteins.Abstract:
STATs (signal transducers and activators of transcription) are a family of latent cytoplasmic proteins that are activated to participate in gene control when cells encounter various extracellular polypeptides. Biochemical and molecular genetic explorations have defined a single tyrosine phosphorylation site and, in a dimeric partner molecule, an Src homology 2 (SH2) phosphotyrosine-binding domain, a DNA interaction domain, and a number of protein-protein interaction domains (with receptors, other transcription factors, the transcription machinery, and perhaps a tyrosine phosphatase). Mouse genetics experiments have defined crucial roles for each known mammalian STAT. The discovery of a STAT in Drosophila , and most recently in Dictyostelium discoideum , implies an ancient evolutionary origin for this dual-function set of proteins.read more
Citations
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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.
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Oncogenic kinase signalling
Peter Blume-Jensen,Tony Hunter +1 more
TL;DR: How oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity is emphasized and an update is provided on the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.
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
Mechanisms of type-I- and type-II-interferon-mediated signalling.
TL;DR: It is anticipated that an increased understanding of the contributions of these recently identified pathways will advance current thinking about how interferons work.
Journal ArticleDOI
Stat3 as an Oncogene
Jacqueline Bromberg,Melissa H. Wrzeszczynska,Geeta Devgan,Yanxiang Zhao,Richard G. Pestell,Chris Albanese,James E. Darnell +6 more
TL;DR: Substitution of two cysteine residues within the C-terminal loop of the SH2 domain of Stat3 produces a molecule that dimerizes spontaneously, binds to DNA, and activates transcription.
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).
Journal ArticleDOI
Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules
Kenneth L. Rock,Colette F. Gramm,Lisa Rothstein,Karen Clark,Ross L. Stein,Lawrence Dick,Daniel Hwang,Alfred L. Goldberg +7 more
TL;DR: Peptide aldehydes that inhibit major peptidase activities of the 20S and 26S proteasomes are shown to reduce the degradation of protein and ubiquitinated protein substrates by 26S particles.
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Phosphorylated CREB binds specifically to the nuclear protein CBP
John C. Chrivia,Roland P. S. Kwok,Ned J.C. Lamb,Masatoshi Hagiwara,Marc Montminy,Richard H. Goodman +5 more
TL;DR: It is proposed that CBP may participate in cAMP-regulated gene expression by interacting with the activated phosphorylated form of CREB, which is activated as a result of phosphorylation by protein kinase A7.
Journal ArticleDOI
Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation.
TL;DR: It is shown that gene activation by Stat1 and Stat3, which obligatorily require tyrosine phosphorylation to become active, also depends for maximal activation on one or more of the many serine kinases.
Journal ArticleDOI
Transcriptional responses to polypeptide ligands: the JAK-STAT pathway.
C Schindler,Jr Je Darnell +1 more
TL;DR: This review will examine how two receptor associated tyrosine kinases from the JAK family mediate the transduction of signal directly from receptor to nucleus.