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Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins

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TLDR
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).
Abstract
Through the study of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), 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 then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-alpha and IFN-gamma pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction.

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Mechanisms and consequences of Jak–STAT signaling in the immune system

TL;DR: Recent advances in Jak–STAT biology are reviewed, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent TFs.
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The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

TL;DR: The mechanism of action of phosphorylation is discussed, with particular attention to the importance ofosphorylation under physiological and pathological conditions, and the possibility of using kinase inhibitors in the treatment of tumors.
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SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity.

TL;DR: The high prevalence of the aberrant SOCS-1 methylation and its growth suppression activity demonstrated the importance of the constitutive activation of the JAK/STAT pathway in the development of HCC.
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2. Cytokines and chemokines.

TL;DR: Cytokines are grouped according to those that are mononuclear phagocytic-derived or T-lymphocyte-derived; that mediate cytotoxic (antiviral and anticancer), humoral, cell-mediated, or allergic immunity; and that are immunosuppressive.
Journal ArticleDOI

Cytokine signaling through nonreceptor protein tyrosine kinases

TL;DR: The intracytoplasmic structure of cytokine receptors has evolved so as to allow the combined action of different PTK family members expressed in different cell types, which may ultimately determine the activity of cytokines.
References
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Journal ArticleDOI

Stimulation of 3T3 cells induces transcription of the c- fos proto-oncogene

TL;DR: Transcription of the c-fos proto-oncogene is greatly increased within minutes of administering purified growth factors to quiescent 3T3 cells, and this stimulation is the most rapid transcriptional response to peptide growth factors yet described, implying a role for c- fos in cell-cycle control.
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Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis

TL;DR: Gel electrophoresis in studies of equilibrium binding, site distribution, and kinetics of protein-DNA interactions found that binding to the so-called third operator site (03) is 15-18 fold weaker than operator binding, and that the binding reactions with the first and third operators are uncoupled, implying that there is no communication between the sites.
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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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SH2 and SH3 Domains: Elements that Control Interactions of Cytoplasmic Signaling Proteins

TL;DR: Observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.
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A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system

TL;DR: It is demonstrated that even when pre-formed in the presence of CAP-cAMP, the polymerase-promoter open complex becomes unstable if CAP is then selectively removed, and this gel method is applied to the study of the E. coli lactose operon regulatory system.
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