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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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Role of the Akt pathway in mRNA translation of interferon-stimulated genes.

TL;DR: Activation of the Akt pathway by the IFN receptors complements the function of IFN-activated JAK–STAT pathways, by allowing mRNA translation ofIFN-stimulated genes and, ultimately, the induction of the biological effects of IFNs.
Journal ArticleDOI

Interferon-α Engages the Insulin Receptor Substrate-1 to Associate with the Phosphatidylinositol 3′-Kinase (∗)

TL;DR: Interferon-α responses occur by activation of the IRS signaling system, which it shares with insulin, insulin-like growth factor-1, and interleukin-4.
Journal ArticleDOI

The IRF family transcription factors at the interface of innate and adaptive immune responses.

TL;DR: Current advances on the multipurpose and critical functions of IRFs in the regulation of innate immunity, particularly as they instruct adaptive immunity are discussed.
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Transforming growth factor beta3 induces cell death during the first stage of mammary gland involution.

TL;DR: Evidence is provided that immediately following weaning TGFbeta3 mRNA and protein is rapidly induced in the mammary epithelium and that this precedes the onset of apoptosis, which is direct evidence that TGF beta3 is a local mammary factor induced by milk stasis that causes apoptosis in the Mammary gland epithelia during involution.
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SH2 and SH3 domains as molecular adhesives: the interactions of Crk and Abl

TL;DR: The Src homology domains SH2 and SH3 are modular components present in many signal transduction proteins that allow rapid formation of stable protein complexes and may also regulate protein function through intramolecular binding events.
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).
Journal ArticleDOI

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.
Journal ArticleDOI

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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