scispace - formally typeset
Journal ArticleDOI

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

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.

read more

Citations
More filters
Journal ArticleDOI

Interleukin 2 and erythropoietin activate STAT5/MGF via distinct pathways.

TL;DR: It is demonstrated that interleukin 2 (IL‐2) as well as erythropoietin (EPO) stimulate STAT5 and induce tyrosine phosphorylation of STAT5, and IL‐4 induces a DNA binding factor which possesses similar, but distinct, DNA binding specificity from that ofSTAT5 and is immunologically different from STAT5.
Journal ArticleDOI

Macrophage polarization and meta-inflammation

TL;DR: The pathogenic alteration of macrophage polarization in meta-inflammation is regulated by both extracellular and intracellular cues, resulting in distinct secretome profiles.
Journal ArticleDOI

Lessons learned from the blockade of immune checkpoints in cancer immunotherapy

TL;DR: The current understanding of the mechanisms by which resistance to checkpoint blockade immunotherapy occurs is summarized, and how actionable combination strategies may be derived to improve clinical outcomes for patients is outlined.
Journal ArticleDOI

Murine Norovirus 1 Infection Is Associated with Histopathological Changes in Immunocompetent Hosts, but Clinical Disease Is Prevented by STAT1-Dependent Interferon Responses

TL;DR: It is demonstrated that murine norovirus infection of wild-type mice is associated with initial enteric seeding and subsequent extraintestinal spread, and mechanistic evidence of the role of STAT-1 in controlling clinical norov virus-induced disease is provided.
References
More filters
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.
Journal ArticleDOI

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.
Journal ArticleDOI

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.
Related Papers (5)