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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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IFNγ sensitizes for apoptosis by upregulating caspase-8 expression through the Stat1 pathway

TL;DR: It is reported that IFNγ sensitizes resistant tumor cells with absent or low caspase-8 expression for apoptosis induced by death-inducing ligands or cytotoxic drugs by upregulating casp enzyme-8 through a Stat1/IRF1 dependent pathway.
Journal ArticleDOI

STAT3 orchestrates contradictory signals in cytokine-induced G1 to S cell-cycle transition

TL;DR: An ‘orchestrating model’ for cytokine and growth factor action is proposed in which contradictory signals are orchestrated to produce a specific effect in a target cell.
Journal ArticleDOI

JAKs, STATs and Src kinases in hematopoiesis.

TL;DR: Cell and tissue-specificity of cytokine action appears to be determined by the nature of signal transduction pathways activated by cytokine/receptor interactions, and the integration of these diverse signaling cues from active JAK kinases, members of the Src-family kinases and STAT proteins, leads to cell proliferation, cell survival and differentiation, the end-point of the cytokin/growth factor stimulus.
Journal ArticleDOI

Interferon-resistant Human Melanoma Cells Are Deficient in ISGF3 Components, STAT1, STAT2, and p48-ISGF3γ

TL;DR: It is concluded that a defect in the level of STAT1 and possibly all three ISGF3 components in IFN-resistant human melanoma cells may be a general phenomenon responsible for reduced cellular responsiveness of melanomas to IFNs.
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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