◀ Back to STAT3
IL12B — STAT3
Pathways - manually collected, often from reviews:
-
NCI Pathway Database IL23-mediated signaling events:
STAT3 (STAT3)
→
IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2)
(modification, collaborate)
Parham et al., J Immunol 2002, Cho et al., J Immunol 2006
Evidence: mutant phenotype, physical interaction, other species
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NCI Pathway Database IL12-mediated signaling events:
STAT3 (STAT3)
→
IL12/IL12R/TYK2/JAK2 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2)
(modification, collaborate)
Jacobson et al., J Exp Med 1995, Zou et al., J Biol Chem 1997
Evidence: assay, other species
-
NCI Pathway Database IL12-mediated signaling events:
IL12/IL12R/TYK2/JAK2 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2)
→
STAT3 (dimer)-active complex (STAT3)
(modification, activates)
Jacobson et al., J Exp Med 1995, Zou et al., J Biol Chem 1997
Evidence: assay, other species
-
NCI Pathway Database IL12-mediated signaling events:
STAT3 (STAT3)
→
IL12/IL12R/TYK2/JAK2 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2)
(modification, collaborate)
Kusaba et al., J Biol Chem 2005
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL23-mediated signaling events:
STAT3 (STAT3)
→
IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2)
(modification, collaborate)
Oppmann et al., Immunity 2000, Parham et al., J Immunol 2002
Evidence: assay, physical interaction
-
NCI Pathway Database IL12-mediated signaling events:
STAT3 (STAT3)
→
IL12/IL12R/TYK2/JAK2 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2)
(modification, collaborate)
Gollob et al., J Immunol 1999
Evidence: mutant phenotype, assay
Text-mined interactions from Literome
Gollob et al., J Immunol 1999
:
A specific inhibitor of p38 MAP kinase completely inhibits the serine phosphorylation of STAT1 and
STAT3 induced by
IL-12 and IL-2 and abrogates the functional synergy between IL-12 and IL-2 without affecting STAT tyrosine phosphorylation
Bright et al., J Immunol 1999
(Encephalomyelitis, Autoimmune, Experimental) :
Inhibition of either Jak-2 or Tyk-2 leads to a decrease in the
IL-12 induced tyrosine phosphorylation of
Stat3 , but not of Stat4, protein
Hoentjen et al., Blood 2005
:
Chromatin immunoprecipitation demonstrated enhanced NF-kappaB ( cRel, RelA ) binding to the
IL-12p40 promoter in IL-10 ( -/- ) but not WT BMDCs. Interestingly, LPS
induced STAT3 phosphorylation in WT but not IL-10 ( -/- ) BMDCs, a process blocked by IL-10 receptor blocking antibody
Muthian et al., J Clin Immunol 2004
(Disease Models, Animal...) :
In vitro treatment of activated T cells with quercetin blocks
IL-12 induced tyrosine phosphorylation of JAK2, TYK2,
STAT3 , and STAT4, resulting in a decrease in IL-12 induced T cell proliferation and Th1 differentiation
Shirota et al., J Immunol 2004
(Autoimmune Diseases) :
Findings indicate that these ODN inhibit IFN-gamma induced STAT1 phosphorylation and
IL-12 induced
STAT3 and STAT4 phosphorylation
Kusaba et al., J Biol Chem 2005
:
IL-12 induced phosphorylation of Stat3 on Ser-727 was affected by rapamycin, which may be due to the effect of rapamycin on the
IL-12 induced interaction between mammalian target of rapamycin (mTOR) and
Stat3
Molenda et al., Mol Immunol 2006
:
In keratinocytes,
IL-12 activates
STAT3 and STAT4 ; surprisingly, despite activating these transcription factors, the transcriptional effects of IL-12 did not rise above background levels
Muthian et al., J Neurosci Res 2006
(Disease Models, Animal...) :
Treatment of activated T cells with 1,25 ( OH ) 2D3 also inhibited the
IL-12 induced tyrosine phosphorylation of JAK2, TYK2,
STAT3 , and STAT4 in association with a decrease in T cell proliferation in vitro
Chen et al., Proc Natl Acad Sci U S A 2006
:
By contrast, Socs3 was found to be a major regulator of
IL-23 mediated
Stat3 phosphorylation and Th17 generation, and Stat3 directly binds to the IL-17A and IL-17F promoters
Li et al., J Immunol 2006
(Encephalomyelitis, Autoimmune, Experimental) :
Indeed, in the present study we found that bone marrow derived DCs transduced with SOCS-3 significantly inhibited IL-12 induced activation of Stat4 and
IL-23 induced activation of
Stat3 ... Indeed, in the present study we found that bone marrow derived DCs transduced with SOCS-3 significantly inhibited
IL-12 induced
activation of Stat4 and IL-23 induced activation of
Stat3
Caruso et al., Eur J Immunol 2008
(Helicobacter Infections) :
Treatment of normal gastric lamina propria mononuclear cells ( LPMC ) with IL-23 enhanced Stat3 activation and IL-17 secretion, and pharmacological inhibition of
Stat3 prevented
IL-23-driven IL-17 synthesis
Stewart et al., Cancer Cell 2009
(Neoplasms) :
In this issue of Cancer Cell, Kortylewski et al. show that in the tumor microenvironment,
STAT3 enhances the expression of the protumor cytokine IL-23 in macrophages but
inhibits the antitumor cytokine
IL-12 in dendritic cells ... In this issue of Cancer Cell, Kortylewski et al. show that in the tumor microenvironment,
STAT3 enhances the expression of the protumor cytokine
IL-23 in macrophages but inhibits the antitumor cytokine IL-12 in dendritic cells
Kortylewski et al., Cancer Cell 2009
(Neoplasms) :
Stat3 induces expression of
IL-23 , which is mainly produced by tumor associated macrophages, via direct transcriptional activation of the IL-23/p19 gene ... Furthermore,
Stat3 inhibits NF-kappaB/c-Rel dependent
IL-12/p35 gene expression in tumor associated dendritic cells
Shanmugarajan et al., J Cell Biochem 2009
:
Chromatin immunoprecipitation ( ChIP ) assay confirmed
STAT-3 , but not STAT-1 binding to the OIP-1 gene promoter in
response to
IL-12 stimulation
Staschke et al., J Immunol 2009
(Encephalomyelitis, Autoimmune, Experimental) :
Furthermore, the absence of IRAK4 kinase activity blocked induction of IL-23R expression,
STAT3 activation by
IL-23 , and Th17 cytokine expression in differentiated Th17 cells
Paradowska-Gorycka et al., Scand J Immunol 2010
(Arthritis, Rheumatoid...) :
IL-23 binding to an IL-23 receptor expressed on dendritic cells, macrophages and monocytes triggers the activation of Jak2 and Tyk2, which in turn phosphorylates STAT1, STAT3, STAT4 and STAT5 as well as
induce formation of
STAT3-STAT4 heterodimers
Jager et al., J Neuroimmunol 2011
(Encephalomyelitis, Autoimmune, Experimental) :
SOCS1-KIR also blocked
IL-23 and IL-17A
activation of
STAT3
Di Meglio et al., PloS one 2011
(Immune System Diseases) :
However, IL-23 mediated Th17 cell effector function was impaired, as Th17 cells from A allele carriers had significantly reduced
IL-23 induced IL-17A production and
STAT3 phosphorylation compared to G allele carriers
Balamayooran et al., Infect Immun 2011
(Escherichia coli Infections...) :
RIP2 ( -/- ) mice also show reduced IL-6 and
IL-23 levels in the lungs, along with decreased
activation of
STAT3 after infection
Pidasheva et al., PloS one 2011
(Genetic Predisposition to Disease...) :
IL23R ( Q381 ) was associated with reduced
STAT3 phosphorylation upon
stimulation with
IL-23 and decreased number of IL-23 responsive T-cells
Floss et al., J Biol Chem 2013
:
In contrast to IL-6 induced short term STAT3 phosphorylation, cellular activation by
IL-23 resulted in a slower but long term
STAT3 phosphorylation, indicating that the IL-23R might not be a major target of negative feedback inhibition by suppressor of cytokine signaling (SOCS) proteins
Jacobson et al., J Exp Med 1995
:
IL-12 selectively
induced nuclear DNA binding complexes that contained
Stat3 and Stat4, recently cloned members of the family of signal transducers and activators of transcription ( STATs )
Yu et al., J Immunol 1996
:
In contrast to IL-2 and IFN-alpha,
IL-12 induced strong tyrosine phosphorylation of STAT4 and variable weak phosphorylation of
STAT3 ... However, supershift analyses using the c-fos promoter sis-inducible element probe showed that
IL-12 activated STAT4, STAT1 alpha, and
STAT3 , and induced complexes containing STAT4 only, STAT4 with STAT1 alpha, STAT3 with STAT1 alpha, or STAT1 alpha only in preactivated primary NK cells