IFNG

Protein IFNG

Identifiers
HUGO:IFNG
interferon gamma
HUGO:IFNG hgnc_id:HGNC:5438 HGNC:5438 ENTREZ:3458 UNIPROT:P01579

Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / CAF_INHIBITION_ANTITUMOR
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_EXPRESSION

References
PMID:21411734 PMID:1825141 PMID:2965306 PMID:24658051 PMID:15811952 PMID:26755705 PMID:16286920 PMID:20819927 PMID:12818165 PMID:15634932 PMID:20038811
PMID:17559085
The Th1 cytokine interferon-?? (IFN-??) inhibits collagen gene transcription, and blocks stimulation induced by TGF-?? (Varga et al., 1990). Negative regulation of collagen gene by IFN-?? plays an important homeostatic role in preventing excessive scar formation. Transcription factors implicated in mediating IFN-??-induced inhibition of collagen gene expression include STAT1?? (Ghosh et al., 2001), class II transactivator (CIITA) (Zhu and Ting, 2001), the RFX5 complex (Sengupta et al., 2002), YB-1 (Higashi et al., 2003), and C/EBP-?? (Ghosh et al., 2006). In our studies focusing on the role of p300 in IFN-?? modulation of collagen synthesis, we found that IFN-?? induced a direct interaction between activated STAT1?? and p300 in normal skin fibroblasts (Ghosh et al., 2001). Furthermore, ectopic expression of p300 overcame the inhibition by IFN-?? and rescued stimulation by TGF-??, suggesting that in response to IFN-??, activated STAT1?? and/or downstream factor(s) sequestered p300, preventing its recruitment to the transcriptional machinery and thereby inhibiting collagen gene transcription (Ghosh et al., 2001). Similarly, IFN-?? suppression of COL1A2 promoter activation by YB-1 also appears to involve p300 sequestration (Higashi et al., 2003).
PMID:12413632
IFNG is a major factor of M1 activation of macrophages.
PMID:6425450
Monoclonal antibody to IFNG inhibits macrophage tumoricidal activities.
PMID:11964313
INFG potentiates TLR signaling and NFkB activation downstream of TLR.
PMID:9864217
IFNG cooperates with TNF and TLR signaling in NF-kB activation.
PMID:19833085
IFNG achieves strong activation effects is by enhancing macrophage
responsiveness to other inflammatory stimuli, such as TLR ligands and TNF.
PMID:14607900, PMID:16713974
IFNG impairs IL-10 anti-inflammatory activity.
PMID:10485906
IFNG downregulates IL4 signaling pathway via SOCS1.
PMID:16713974
INFG signaling inhibits p38 activation
PMID:15814715, PMID:18272812, PMID:17016554
STAT1 is involeved in immunosupresive activity of M2 macrophages and MDSC, probably downstream of IFNG.
activation of MSCs is initiated in response to IFN-gamma, presumably produced in situ by antitumor T cells in the tumor microenvironment.
PMID:16424049
The secretion of interleukin (IL)-10 and transforming growth factor-beta by Gr-1(+)CD115(+) MSCs and iNOS expression was induced and enhanced, respectively, on IFN-gamma stimulation.
PMID:11870632, PMID:9834059
Stimulation of??NK??cells??with IL-4 inhibited IFN-gamma, but increased IL5, IL-13 expression.
NK cells stimuletad by IL4 have NK2 subtype
PMID:21149606
Nkp80 signaling induces marked IFNG production
PMID:11777960
ULBP2 through NKG2D induces SCF2 (GM-CSF), CLL4 (MIP1B) and IFNG secretion via PI3K pathway
PMID:11489965, PMID:15778339
KIR2DL4 transduces signals into human NK cells through association with the Fc receptor gamma protein. It induces IFNG production but not cytotoxicity in resting NK cells
PMID:16713974, PMID:11579131
INFG pathway inhibits activation (phosphorylation) of ERK, JNK, p38 kinases and PI3K pathway induced by TLR. Inhibition of AKT pathway by IFNG resulted in activation of GSK3. GSK3 inhibits downstream AP-1 and CREB1 signaling and downregulates IL10 expression induced by TLR.IFNG inhibits CREB activation via p38 induced by TLR signaling

IFNG|hm2@default

References
in_re163( Innate Immunity ):
PMID:16713974
TLR signaling activates and IFNG inhibits PI3K pathway
PMID:11907067, PMID:15536084
SYK kinaze directly interacts with PI3K(p85) and activates perforin ??granule movement and polarization via PI3K /RAC1/PAK1/MEK??/ERK pathway
PMID:10426994??
Phosphorylated DAP10 directly interacts with regulatory subunit (p85) of PI3K and activates downstream pathway.
in_re423( Innate Immunity ):
PMID:20547845
TLR4 signaling downstream of HMGB1 induces secretion of IL10
RNAi-mediated knockdown of CREB, Fos, and Jun expression resulted in diminished TLR2-induced IL-10 production
GSK3B inhitits activation (DNA binding) of AP-1 factors.
JNK is a classical activator of AP1 transcription factors.
Inhibition of JNK downregulates IL10 expression. Probably via
AP1.
PMID:17404308
CSF1 upregulates expression of IL10 and CCL2 probably via CSF1R.
PMID:15749884
c-Maf binds to the ???206/???171 region in the IL-10 promoter and upregulates IL10 expression.
in_re427( Innate Immunity ):
Production of IL10 is partially ERK dependent.
in_re701( Innate Immunity ):
PMID:11964313, PMID:11672593, PMID:12811837.
INFG upregulates mRNA level and surface expression of TLR4 and TLR2.
in_re702( Innate Immunity ):
PMID:16267105
Exposure of macrofages to HMGB1 resulted in rapid decreases in protein level of both TLR2 and TLR4??receptors.
PMID:11672593
CSF1 up-regulates both TLR2 and TLR4 surface expression
in_re703( Innate Immunity ):
PMID:11964313, PMID:11672593, PMID:12032143, PMID:12811837.
in_re713( Innate Immunity ):
PMID:11964313
INFG upregulates expression components of TLR signaling: MD2 (LY96) and MYD88.
in_re729( Innate Immunity ):
PMID:14607933
TNF induces the association of STAT-1 and TNFR1 in a tyrosine phosphorylation-independent manner, and and this association attenuates TNF-alpha-mediated NF-kappaB activation but formation of the TNFR1:STAT-1?? complex is inhibited upon inclusion of IFNG . IFNG limits STAT-1 availability to the TNFR1 by depleting STAT from the cytoplasm, thus allowing for optimal NF-kappaB activation upon TNF ligation.
in_re929( Innate Immunity ):
TLR2 activates (induces phosphorylation of) ERKs, JNKs, and p38 rapidly and transiently in control macrophages.
This activation is inhibited by IFNG signaling.
PMID:11438547, PMID:24378531
Both TNFR1 and TNFR2 signaling pathways induce JNK activation and downstrean c-jun phosphorylation.
in_re930( Innate Immunity ):
PMID:11875494
IL10-induced p38 phosphorylation.
PMID:20435894
SHIP inhibit MAPKp38 activation and prevent
MKNK1 phosphorylation by inhibiting the p38MAPK
pathway downstream of IL10.
PMID:10925299
IL13 induces p38 MAPK phosphorilation and activation, p38 MAPK participates in arginase activation??downstream of IL13.
PMID:23508573
HMGB1 induces activation (phosphorylation) of p38 via TLR4.
PMID:12811837, PMID:16713974
TLR signaling can induces STAT1 phosphorylation via p38 and potentiate IFNG signaling.
Both TNFR1 and TNFR2 signaling pathways are needed for activation of p38 MAPK.
in_re1279( Innate Immunity ):
PMID:8641346
IFNG did not affect the??expression??of p105 transcripts but enhanced the??expression??of p65??mRNA.

Modifications:
In compartment: INNATE_IMMUNE_CELL_Cytosol

IFNG@INNATE_IMMUNE_CELL_Cytosol

In compartment: default

IFNG@default
IFNG|hm2@default

Participates in complexes:
In compartment: INNATE_IMMUNE_CELL_Membrane

IFNGR1|pho:IFNGR2:IFNG|hm2:JAK1:JAK2@INNATE_IMMUNE_CELL_Membrane

Participates in reactions:
As Reactant or Product:

As Catalyser: