Journal ArticleDOI
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.read more
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Interferon-γ-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression
Roberto Bellucci,Allison Martin,Davide Bommarito,Kathy K. Wang,Steen H. Hansen,Gordon J. Freeman,Jerome Ritz +6 more
TL;DR: The results show that NK cell activation and secretion of IFNγ results in activation of JAK1, JAK2 and STAT1 in tumor cells, resulting in rapid up-regulation of PD-L1 expression, suggesting that JAK pathway inhibitors as well as PD-1 and PD- L1 antibodies may work synergistically with other immune therapies by preventing IFN-induced inhibition of NK cell-mediated tumor cell lysis.
Journal ArticleDOI
Ischemia-induced STAT-1 Expression and Activation Play a Critical Role in Cardiomyocyte Apoptosis
Anastasis Stephanou,Bhawanjit K. Brar,Tiziano M. Scarabelli,AK Jonassen,Derick M. Yellon,Michael S. Marber,Richard A. Knight,David S. Latchman +7 more
TL;DR: It is shown that exposure of cardiac cells to simulated ischemia results in apoptosis and is accompanied by phosphorylation and increased expression and transcriptional activity of STAT-1, acting at least in part via a caspase-1 activation-dependent pathway.
Journal ArticleDOI
Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor
M. Showkat Ali,Peter P. Sayeski,Laurie B. Dirksen,David J. Hayzer,Mario B. Marrero,Kenneth E. Bernstein +5 more
TL;DR: The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intrace cellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors.
Journal ArticleDOI
Tyrosine-phosphorylated Stat1 and Stat2 plus a 48-kDa protein all contact DNA in forming interferon-stimulated-gene factor 3.
TL;DR: Evidence is presented that a heterodimer of Stat1 and Stat2 is present in ISGF3 and that Stat 1 and the 48-kDa protein make precise contact, while Stat2 makes general contact, with the interferon-stimulated response element, the binding site of the IsGF3.
Journal ArticleDOI
GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction
Chengchen Lufei,Jing Ma,Guochang Huang,Tong Zhang,Veronica Novotny-Diermayr,Chin Thing Ong,Xinmin Cao +6 more
TL;DR: The data suggest that GRIM‐19 is a novel negative regulator of Stat3, which inhibits Stat3 nuclear translocation stimulated by epidermal growth factor (EGF) and suppresses cell growth in Src‐transformed cells and a Stat3‐expressing cell line.
References
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Journal ArticleDOI
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Journal ArticleDOI
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Journal ArticleDOI
SH2 and SH3 Domains: Elements that Control Interactions of Cytoplasmic Signaling Proteins
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Journal ArticleDOI
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