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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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Distinct STAT Structure Promotes Interaction of STAT2 with the p48 Subunit of the Interferon-α-stimulated Transcription Factor ISGF3

TL;DR: Evidence that STAT2 specifically interacts with p48 in vivo before and after IFN-α stimulation is provided and data suggest that distinct bipartite complexes STAT2·p48 andSTAT2·STAT1 translocate to the nucleus and associate on the DNA target site as ISGF3.
Journal ArticleDOI

Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3.

TL;DR: The increasing understanding of c-Kit and Flt3 signaling has also revealed the complexity of these receptor systems, and targeted therapy using a combination of such inhibitors is considered a promising approach for future treatments.
Journal ArticleDOI

Stat1-vitamin D receptor interactions antagonize 1,25-dihydroxyvitamin D transcriptional activity and enhance stat1-mediated transcription.

TL;DR: This novel 1,25D-IFN-γ cross talk explains the pathogenesis of abnormal 1, 25D homeostasis in granulomatous processes and provides new insights into 1-25D immunomodulatory properties.
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Activation of Stat3 Signaling in AgRP Neurons Promotes Locomotor Activity

TL;DR: Mice expressing a constitutively active version of Stat3 selectively in AgRP neurons are lean and exhibit relative resistance to diet-induced obesity, Surprisingly, this phenotype arises from increased locomotor activity in the presence of unaltered AgRP expression.
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Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program

TL;DR: It is shown that Fcγ receptor (FcγR)–mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene expression pattern, including several inflammation-associated chemokines, as well as type 1 interferon (IFN) response genes, including the activation of signal transducer and activation of transcription 1 (STAT1).
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.
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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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