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proteins. Page last changed on 14 Mar 2013.
Signal transducer and activator of transcription 4
STAT4, signal transducer and activator of transcription 4
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is essential for mediating responses to IL12 in lymphocytes, and regulating the differentiation of T helper cells. Mutations in this gene may be associated with systemic lupus erythematosus and rheumatoid arthritis. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2011] (from
NCBI)
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Papers using
STAT4
antibodies
Regulation of T cell receptor expression in immature CD4+CD8+thymocytes by p56lck tyrosine kinase: basis for differential signaling by CD4 and CD8 in immature thymocytes expressing both coreceptor molecules
Supplier
In The Journal of Experimental Medicine, 1992
... Stat4-deficient DO11.10 TCR-transgenic mice have been described ...
Papers on
STAT4
IL-12 receptor β1 deficiency alters in vivo T follicular helper cell response in humans.
New
Dallas, United States. In Blood, 08 Apr 2013
Key points IL-12Rβ1 deficient subjects displayed substantially less circulating memory Tfh and memory B cells than control subjects.The IL-12-STAT4 axis is associated with the development and the functions of Tfh cells in vivo in humans.
Protective role of synthetic oligodeoxynucleotides expressing immunosuppressive TTAGGG motifs in Concanavalin A-induced hepatitis.
New
Changsha, China. In Immunol Lett, 04 Apr 2013
In the splenic lymphocytes, Western blot analysis showed that suppressive ODNs down-regulated the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT4, and suppressed up-regulation of T-bet, but didn't impact the phosphorylation of STAT6 which are associated with a Th2 phenotype.
Rheumatoid arthritis in Latin Americans enriched for Amerindian ancestry is associated with loci in chromosomes 1, 12,13, and HLA class II region.
New
Granada, Spain. In Arthritis Rheum, 04 Apr 2013
We identified onenovel putative association in ENOX1onchromosome 13 (p= 7.0 × 10-7 ).Previously reported RA associations were observed, with moderate p values (>x10-5 ), including STAT4, IRF5, IL2RA, SPRED2, CCL21 and PTPN22.Adjustment for Amerindian ancestryimproved the association of a novel locus in chromosome 12, atC12orf30 (NNA25) (p= 3.9 × 10-6 ).
Susceptibility to childhood onset rheumatoid arthritis: Investigation of a weighted genetic risk score that integrates cumulative effects of variants at five genetic loci.
New
Gambia. In Arthritis Rheum, 28 Mar 2013
METHODS: 155 children with CORA and 684healthy controls were genotyped for fivevariants in PTPN22, TRAF1/C5, STAT4, and TNFAIP3 loci.
Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1.
New
Impact
Bethesda, United States. In Nat Genet, 28 Feb 2013
We identified new associations at CCR1, STAT4 and KLRC4.
Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma.
New
Impact
Shanghai, China. In Nat Genet, Jan 2013
The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49.
T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor β2.
New
Impact
Seattle, United States. In Immunity, Oct 2012
Additionally, delayed induction of the IL-12Rβ2 receptor component after STAT1 activation helped ensure that Treg cells do not readily complete STAT4-dependent Th1 cell development and lose their ability to suppress effector T cell proliferation.
Primary Sjögren's syndrome and the type I interferon system.
Review
New
Uppsala, Sweden. In Curr Pharm Biotechnol, Aug 2012
Polymorphisms in the interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) genes in the type I IFN system, are associated with increased risk for pSS.
Transcriptional mechanisms that regulate T helper 1 cell differentiation.
Review
New
Seattle, United States. In Curr Opin Immunol, Apr 2012
In particular, studies examining the transcription factors T-bet, STAT1, and STAT4 have elucidated their roles in regulating Th1 signature genes, including Ifng, and have started to address their contributions to the epigenetic states in Th1 cells.
The composition and signaling of the IL-35 receptor are unconventional.
New
Impact
Memphis, United States. In Nat Immunol, Mar 2012
Signaling through the IL-35 receptor required the transcription factors STAT1 and STAT4, which formed a unique heterodimer that bound to distinct sites in the promoters of the genes encoding the IL-12 subunits p35 and Ebi3.
Early Th1 cell differentiation is marked by a Tfh cell-like transition.
Impact
Bethesda, United States. In Immunity, 2012
Herein, we showed interleukin-12 acting via the transcription factor STAT4 induced both Il21 and Bcl6 genes, generating cells with features of both Tfh and Th1 cells.
Natural killer cell functional dichotomy: a feature of chronic viral hepatitis?
Pavia, Italy. In Front Immunol, 2011
In chronic HCV infection this appears to be caused by altered IFN-α signaling resulting from increased signal transducer and activator of transcription 1 (STAT1) phosphorylation, which polarizes NK cells toward cytotoxicity, and a concomitantly reduced IFN-α induced STAT4 phosphorylation yielding reduced IFN-γ mRNA levels.
The type I interferon system in the etiopathogenesis of autoimmune diseases.
Review
Uppsala, Sweden. In Ups J Med Sci, 2011
Among these autoimmunity risk genes are IFN regulatory factor 5 (IRF5), which is involved in TLR signaling, and the signal transducer and activator of transcription 4 (STAT4) that interacts with the type I IFN receptor.
SDF-1/CXCR4 mediates acute protection of cardiac function through myocardial STAT3 signaling following global ischemia/reperfusion injury.
GeneRIF
Indianapolis, United States. In Am J Physiol Heart Circ Physiol, 2011
Our results represent the first evidence that the SDF-1/CXCR4 axis upregualtes myocardial STAT3 activation
Signal transducer and activator of transcription 4 gene polymorphisms associated with rheumatoid arthritis in Northwestern Chinese Han population.
GeneRIF
Lanzhou, China. In Life Sci, 2011
These findings strongly suggest that STAT4 genetic polymorphisms are associated with rheumatoid arthritis in Northwestern Chinese Han population
Interleukin-12 treatment down-regulates STAT4 and induces apoptosis with increasing ROS production in human natural killer cells.
GeneRIF
Rockville, United States. In J Leukoc Biol, 2011
prolonged IL-12 stimulation of NK cells specifically decreases the level of activated STAT4 protein
An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation.
Review
Bethesda, United States. In Int Immunol, 2011
On the other hand, GATA3 inhibits T(h)1 cell differentiation by preventing up-regulation of IL-12 receptor β2 and STAT4 (signal transducer and activator of transcription 4) and neutralization of Runx3 (runt-related transcription factor 3) function through protein-protein interaction.
Stat4 is critical for the balance between Th17 cells and regulatory T cells in colitis.
GeneRIF
Baltimore, United States. In J Immunol, 2011
Results highlight the critical role of Stat4 Th1 signals in autoimmune responses in suppressing Foxp3(+) Treg responses and altering the balance between Th17 and Tregs to favor autoimmune disease.
STAT4 is required for IFN-β-induced MCP-1 mRNA expression in murine mast cells.
GeneRIF
Chiba, Japan. In Int Arch Allergy Immunol, 2010
STAT4 plays an essential role in IFN-beta-induced MCP-1 mRNA expression in mast cells.
Aspects of innate immunity in Sjögren's syndrome.
Review
Hannover, Germany. In Arthritis Res Ther, 2010
Polymorphisms in the genes IRF5 and STAT4 leading to increased IFN activation are associated with disease susceptibility.
