Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes.
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IL-12 induces tyrosine phosphorylation and nuclear translocation of STAT4 in human T and NK cells.
"IL-12 induces tyrosine phosphorylation of a recently identified STAT family member, STAT4, and show that STAT4 expression is regulated by T-cell activation. Furthermore, we show that IL-12 stimulates formation of a DNA-binding complex that recognizes a DNA sequence previously shown to bind STAT proteins and that this complex contains STAT4"
cDNA cloning, expression and chromosome mapping of the human STAT4 gene: both STAT4 and STAT1 genes are mapped to 2q32.2-->q32.3.
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STAT4 is a STAT-family transcription factor essential for IL-12 signal transduction, expressed in spleen, heart, brain, peripheral blood cells, and testis.
"STAT4 is phosphorylated following interleukin (IL)-12 stimulation and is essential for IL-12 signal transduction... human STAT4 is expressed in several tissues including spleen, heart, brain, peripheral blood cells, and testis"
Importance of the MKK6/p38 pathway for interleukin-12-induced STAT4 serine phosphorylation and transcriptional activity.
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MAP2K6/p38 phosphorylates STAT4 at Ser-721, which is required for full transcriptional activity but not DNA binding.
"IL-12 induces STAT4 phosphorylation on serine 721 and that mutation of serine 721 interferes with STAT4 transcriptional activity"
STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation.
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STAT4 Ser-721 phosphorylation is critical for IFN-gamma production but not for cell proliferation.
"expression of wild-type STAT4, but not the S721A mutant, restored normal T(H)1 differentiation and IFN-gamma synthesis"
Sustained IL-12 signaling is required for Th1 development.
Mechanisms of type-I- and type-II-interferon-mediated signalling.
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Review of JAK-STAT signaling in interferon responses including STAT4 activation.
"the classical JAK (Janus activated kinase)-STAT (signal transducer and activator of transcription) pathway of signalling"
Tyrosine phosphorylation regulates the partitioning of STAT1 between different dimer conformations.
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STAT4 forms homodimers detected by IntAct.
"the N-domain dissociation constants of STAT1, STAT3, and STAT4 differed by more than three orders of magnitude"
The oncoprotein HBXIP uses two pathways to up-regulate S100A4 in promotion of growth and migration of breast cancer cells.
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STAT4 interacts with LAMTOR5 detected by IntAct.
"HBXIP is able to activate S100A4 promoter via interacting with STAT4 in breast cancer cells, leading to the up-regulation of S100A4"
STAT heterodimers in immunity: A mixed message or a unique signal?
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IL-12 induces mostly STAT4 homodimers; IL-23 promotes STAT3:STAT4 heterodimers; IL-35 induces STAT1:STAT4 heterodimers.
"IL-12 works mainly through inducing mostly STAT4 homodimers... IL-23 was shown to activate STAT3 and STAT4 downstream of these receptors... IL-35 utilizes three receptors... the gp130:IL-12Rbeta2 heterodimeric receptor is essential for induced expression of IL-35, which is initiated by a STAT1:STAT4 heterodimer"
STAT4-mediated transcriptional repression of the IL5 gene in human memory Th2 cells.
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STAT4 acts as a transcriptional repressor of IL5 in response to IFN-alpha/beta signaling.
"IFN-α/β-mediated STAT4 activation was required for repressing the human IL5 gene, and disrupting STAT4 dimerization reversed this effect. This is the first demonstration of STAT4 acting as a transcriptional repressor in response to IFN-α/β signaling"
STAT4 Directs a Protective Innate Lymphoid Cell Response to Gastrointestinal Infection.
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Direct assay evidence for STAT4 DNA-binding transcription factor activity.
"the transcription factor STAT4 is required for the proliferative and IFN-γ effector response by ILC1s and ILC3s, and loss of STAT4 signaling in the innate immune compartment results in an inability to control bacterial growth and dissemination. Interestingly, STAT4 acts acutely as a transcription factor to promote IFN-γ production"
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
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High-throughput yeast two-hybrid interactome mapping detecting STAT4 interactions with KLF11 and NUP58.
"Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions"
Acetylation licenses Th1 cell polarization to constrain Listeria monocytogenes infection.
Variant STAT4 and Response to Ruxolitinib in an Autoinflammatory Syndrome.
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Gain-of-function STAT4 SH2 domain variants (H623Y, A635V, A650D) cause disabling pansclerotic morphea of childhood (DPMC) with constitutive JAK-STAT signaling.
"Genome sequencing revealed three novel heterozygous missense gain-of-function variants in STAT4"
p-Y693-STAT4 dimer translocates to the nucleus
STAT3, STAT4 are phosphorylated by p-JAK2, p-TYK2 in IL23:IL23 receptor
STAT4 binds to IL12RB2 in Interleukin-12 receptor complex
JAK1/JAK2 bound to IL12RB2:IL6ST receptor phosphorylates STAT1 and STAT4
p-STAT1:p-STAT4 translocates to the nucleus
p-Y705-STAT3:p-Y693-STAT4 translocates to the nucleus
p-Y705-STAT3 binds p-Y693-STAT4
STAT4 binds p-Y-IL23R in IL23:IL23 receptor
p-Y693-STAT4 dissociates after IL12:IL12R interaction
p-Y693-STAT4, p-Y705-STAT3 dissociate from IL23:IL23 receptor
JAK2 bound to IL12RB2:IL12RB2 phosphorylate STAT4
STAT4 binds IL12RB2:IL12RB2
p-STAT4 dissociates from IL12RB2:IL12RB2 receptor
p-STAT1 and p-STAT4 dissociate from IL12RB2:IL6ST receptor
STAT1 and STAT4 associate with IL12RB2:IL6ST receptor
IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:STAT1 phosphorylates STAT1, STAT2, STAT3, STAT4 and STAT5
p-STAT1, p-Y-STAT2, p-STAT3, p-STAT4, p-STAT5 dissociates from IFNL receptor complex
IFNL1:p-Y434,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2 binds STAT1, STAT2, STAT3, STAT4, STAT5
IL21 receptor STAT phosphorylation
IL21 receptor STAT binding