Interferon gamma signaling (Homo sapiens)

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23, 26, 45, 506, 46, 484, 22, 243, 1511, 17, 19, 27, 30...13, 294, 24, 4110, 14, 19, 3536, 378, 18, 20, 25, 38...9, 16, 32, 462, 7, 28, 345, 31, 3391, 12nucleoplasmlysosomal lumenendoplasmic reticulum lumencytosolIFNG IFN-gammaupregulated CAMsGAS promoter regionin IFNG-regulatedgenesSUMO1p-Y1007-JAK2 IFNG homodimerp-S727,Y701-STAT1-1 SOCS3 HLA class IIhistocompatibilityantigen, DRB1-14beta chain STAT1-1IFNGR1 SUMO1 MHC class IIalpha/beta dimerp-Y440-IFNGR1 IFNG p-S727,Y701-STAT1-1 IFNG p-STAT1dimer:PIAS:SUMO1JAK2 IFNG-activatedfactor (GAF)JAK1 IFNGR2 CaMKII and PKC-deltaPip-STAT1 dimer boundto p-IFNGR1p-S727,Y701-STAT1-1 p-Y-JAK1 IFNG:IFNGR1:JAK1:IFNGR2:JAK2IFNGR2 IFNGR1 p-S727,Y701-STAT1-1 HLA class IIhistocompatibilityantigen, DQ PTPs-SHP1/2/PTP1BIFNGR1 p-Y-JAK1 p-Y1007-JAK2 IFNG SOCS1 IFNGR2 Pip-Y440-IFNGR1 HLA class IIhistocompatibilityantigen, DR beta 4chain PMLp-Y-JAK1 PTPN6PTAFRPIAS1 ADPIFNG ATPH2OIFNG GBPIFI30JAK2 ATPPIAS1H2OHLA class IIhistocompatibilityantigen, DRB1-7beta chain IFNGR2 HLA class IIhistocompatibilityantigen, DRB1-4beta chain SP100p-Y440-IFNGR1 HLA class IIhistocompatibilityantigen, DRB1-8beta chain p-Y1007-JAK2 PTPN1SOCS-1 and SOCS-3HLA class IIhistocompatibilityantigen, DRB1-15beta chain HLA class IIhistocompatibilityantigen, DRB1-10beta chain HLA class IIhistocompatibilityantigen, DR alphachain precursor JAK1 IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2:SOCS-1/-3p-Y-JAK1 p-Y440-IFNGR1 IFNGR2 JAK1 FCGRAp-S727,Y701-STAT1-1 p-STAT1(Y701) boundto p-IFNGR1IFNGR2 IFNG-activatedfactor (GAF)IFNG INFG induced TRIMsIFNGR2 HLA class IIhistocompatibilityantigen, DRB1-9beta chainprecursor ATPIRF 1-9p-Y701-STAT1-1 OAS proteinsIFNG IFNGR1 HLA class IIhistocompatibilityantigen, DQ beta 2chain ADPIFNGR2 ADPCIITAADPHLA class IIhistocompatibilityantigen, DRB1-13beta chain HLA class IIhistocompatibilityantigen, DRB1-1beta chain HLA class IIhistocompatibilityantigen, DP alphachain precursor p-Y1007-JAK2 IFNG ADPIFNGR1:JAK1:INFG2:JAK2STAT1 bound top-IFNGR1HLA class IIhistocompatibilityantigen, DRB3-1beta chainprecursor HLA class IIhistocompatibilityantigen, DRB1-12beta chain IFNGR2 HLA class IIhistocompatibilityantigen, DP HLA class IIhistocompatibilityantigen, DQB1*0602beta chainprecursor p-Y-JAK1 p-Y1007-JAK2 B2M(21-119)IFNGR1 STAT1-1HLA class IIhistocompatibilityantigen, DR-1 betachain precursor ATPHLA class IIhistocompatibilityantigen, DR beta 5chain IFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2STAT1-1 MT2AHLA class IIhistocompatibilityantigen, DRB1-11beta chain PTPN2-1HLA class IIhistocompatibilityantigen, DQ JAK1 IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2HLA class IIhistocompatibilityantigen, DQ HLA class IIhistocompatibilityantigen, DRB1-16beta chain ATPGAF bound to GASpromoter elementp-Y1007-JAK2 p-Y1007-JAK2 IFNG:p-IFNGR1:p-JAK1:IFNGR2:p-JAK2Class I MHC heavychain (MHC HC)18, 2540, 47, 4927, 3921


Description

Interferon-gamma (IFN-gamma) belongs to the type II interferon family and is secreted by activated immune cells-primarily T and NK cells, but also B-cells and APC. INFG exerts its effect on cells by interacting with the specific IFN-gamma receptor (IFNGR). IFNGR consists of two chains, namely IFNGR1 (also known as the IFNGR alpha chain) and IFNGR2 (also known as the IFNGR beta chain). IFNGR1 is the ligand binding receptor and is required but not sufficient for signal transduction, whereas IFNGR2 do not bind IFNG independently but mainly plays a role in IFNG signaling and is generally the limiting factor in IFNG responsiveness. Both IFNGR chains lack intrinsic kinase/phosphatase activity and thus rely on other signaling proteins like Janus-activated kinase 1 (JAK1), JAK2 and Signal transducer and activator of transcription 1 (STAT-1) for signal transduction. IFNGR complex in its resting state is a preformed tetramer and upon IFNG association undergoes a conformational change. This conformational change induces the phosphorylation and activation of JAK1, JAK2, and STAT1 which in turn induces genes containing the gamma-interferon activation sequence (GAS) in the promoter. Source:Reactome.

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Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
115093view17:04, 25 January 2021ReactomeTeamReactome version 75
113535view12:01, 2 November 2020ReactomeTeamReactome version 74
112733view16:13, 9 October 2020ReactomeTeamReactome version 73
101649view11:51, 1 November 2018ReactomeTeamreactome version 66
101185view21:39, 31 October 2018ReactomeTeamreactome version 65
100711view20:11, 31 October 2018ReactomeTeamreactome version 64
100261view16:56, 31 October 2018ReactomeTeamreactome version 63
99814view15:20, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99357view12:48, 31 October 2018ReactomeTeamreactome version 62
93905view13:44, 16 August 2017ReactomeTeamreactome version 61
93478view11:24, 9 August 2017ReactomeTeamreactome version 61
86576view09:21, 11 July 2016ReactomeTeamreactome version 56
83234view10:27, 18 November 2015ReactomeTeamVersion54
81633view13:10, 21 August 2015ReactomeTeamVersion53
77096view08:39, 17 July 2014ReactomeTeamFixed remaining interactions
76802view12:18, 16 July 2014ReactomeTeamFixed remaining interactions
76125view10:19, 11 June 2014ReactomeTeamRe-fixing comment source
75837view11:40, 10 June 2014ReactomeTeamReactome 48 Update
75198view09:43, 9 May 2014AnweshaFixing comment source for displaying WikiPathways description
74845view10:07, 30 April 2014ReactomeTeamReactome46
44865view09:58, 6 October 2011MartijnVanIerselOntology Term : 'immune response pathway' added !
42056view21:53, 4 March 2011MaintBotAutomatic update
39862view05:53, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
B2M(21-119)ProteinP61769 (Uniprot-TrEMBL)
CIITAProteinP33076 (Uniprot-TrEMBL)
CaMKII and PKC-deltaR-HSA-909568 (Reactome)
Class I MHC heavy chain (MHC HC)R-HSA-983117 (Reactome)
FCGRAR-HSA-1031694 (Reactome)
GAF bound to GAS promoter elementComplexR-HSA-1031710 (Reactome)
GAS promoter region

in IFNG-regulated

genes		R-NUL-1031708 (Reactome)
GBPR-HSA-1031695 (Reactome)
H2OMetaboliteCHEBI:15377 (ChEBI)
HLA class II

histocompatibility

antigen, DP 		ProteinP04440 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DP alpha

chain precursor 		ProteinP20036 (Uniprot-TrEMBL)
HLA class II

histocompatibility

antigen, DQ 		ProteinP01906 (Uniprot-TrEMBL)
HLA class II

histocompatibility

antigen, DQ 		ProteinP01909 (Uniprot-TrEMBL)
HLA class II

histocompatibility

antigen, DQ 		ProteinP01920 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DQ beta 2

chain 		ProteinP05538 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DQB1*0602 beta chain

precursor 		ProteinP01920 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DR alpha

chain precursor 		ProteinP01903 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DR beta 4

chain 		ProteinP13762 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DR beta 5

chain 		ProteinQ30154 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DR-1 beta

chain precursor 		ProteinP01912 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-1

beta chain 		ProteinP04229 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-10

beta chain 		ProteinQ30167 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-11

beta chain 		ProteinP20039 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-12

beta chain 		ProteinQ95IE3 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-13

beta chain 		ProteinQ5Y7A7 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-14

beta chain 		ProteinQ9GIY3 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-15

beta chain 		ProteinP01911 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-16

beta chain 		ProteinQ29974 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-4

beta chain 		ProteinP13760 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-7

beta chain 		ProteinP13761 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-8

beta chain 		ProteinQ30134 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-9 beta chain

precursor 		ProteinQ9TQE0 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB3-1 beta chain

precursor 		ProteinP79483 (Uniprot-TrEMBL)
IFI30ProteinP13284 (Uniprot-TrEMBL)
IFN-gamma upregulated CAMsR-HSA-1031690 (Reactome)
IFNG ProteinP01579 (Uniprot-TrEMBL)
IFNG homodimerComplexR-HSA-873823 (Reactome)
IFNG-activated factor (GAF)ComplexR-HSA-873824 (Reactome)
IFNG-activated factor (GAF)ComplexR-HSA-873827 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:JAK2ComplexR-HSA-873829 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2:SOCS-1/-3ComplexR-HSA-873821 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2ComplexR-HSA-873811 (Reactome)
IFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2ComplexR-HSA-873820 (Reactome)
IFNG:p-IFNGR1:p-JAK1:IFNGR2:p-JAK2ComplexR-HSA-873814 (Reactome)
IFNGR1 ProteinP15260 (Uniprot-TrEMBL)
IFNGR1:JAK1:INFG2:JAK2ComplexR-HSA-873810 (Reactome)
IFNGR2 ProteinP38484 (Uniprot-TrEMBL)
INFG induced TRIMsR-HSA-5624346 (Reactome)
IRF 1-9R-HSA-1015695 (Reactome)
JAK1 ProteinP23458 (Uniprot-TrEMBL)
JAK2 ProteinO60674 (Uniprot-TrEMBL)
MHC class II alpha/beta dimerComplexR-HSA-2213189 (Reactome)
MT2AProteinP02795 (Uniprot-TrEMBL)
OAS proteinsR-HSA-1015696 (Reactome)
PIAS1 ProteinO75925 (Uniprot-TrEMBL)
PIAS1ProteinO75925 (Uniprot-TrEMBL)
PMLProteinP29590 (Uniprot-TrEMBL)
PTAFRProteinP25105 (Uniprot-TrEMBL)
PTPN1ProteinP18031 (Uniprot-TrEMBL)
PTPN2-1ProteinP17706-2 (Uniprot-TrEMBL)
PTPN6ProteinP29350 (Uniprot-TrEMBL)
PTPs-SHP1/2/PTP1BR-HSA-997298 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
SOCS-1 and SOCS-3R-HSA-877267 (Reactome)
SOCS1 ProteinO15524 (Uniprot-TrEMBL)
SOCS3 ProteinO14543 (Uniprot-TrEMBL)
SP100ProteinP23497 (Uniprot-TrEMBL)
STAT1 bound to p-IFNGR1ComplexR-HSA-873828 (Reactome)
STAT1-1 ProteinP42224-1 (Uniprot-TrEMBL)
STAT1-1ProteinP42224-1 (Uniprot-TrEMBL)
SUMO1 ProteinP63165 (Uniprot-TrEMBL)
SUMO1ProteinP63165 (Uniprot-TrEMBL)
p-S727,Y701-STAT1-1 ProteinP42224-1 (Uniprot-TrEMBL)
p-STAT1 dimer:PIAS:SUMO1ComplexR-HSA-877297 (Reactome)
p-STAT1 dimer bound to p-IFNGR1ComplexR-HSA-909556 (Reactome)
p-STAT1(Y701) bound to p-IFNGR1ComplexR-HSA-873817 (Reactome)
p-Y-JAK1 ProteinP23458 (Uniprot-TrEMBL)
p-Y1007-JAK2 ProteinO60674 (Uniprot-TrEMBL)
p-Y440-IFNGR1 ProteinP15260 (Uniprot-TrEMBL)
p-Y701-STAT1-1 ProteinP42224-1 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-873918 (Reactome)
ADPArrowR-HSA-873919 (Reactome)
ADPArrowR-HSA-873922 (Reactome)
ADPArrowR-HSA-873924 (Reactome)
ADPArrowR-HSA-909552 (Reactome)
ATPR-HSA-873918 (Reactome)
ATPR-HSA-873919 (Reactome)
ATPR-HSA-873922 (Reactome)
ATPR-HSA-873924 (Reactome)
ATPR-HSA-909552 (Reactome)
B2M(21-119)ArrowR-HSA-1031716 (Reactome)
CIITAArrowR-HSA-1031716 (Reactome)
CaMKII and PKC-deltamim-catalysisR-HSA-909552 (Reactome)
Class I MHC heavy chain (MHC HC)ArrowR-HSA-1031716 (Reactome)
FCGRAArrowR-HSA-1031716 (Reactome)
GAF bound to GAS promoter elementArrowR-HSA-1031713 (Reactome)
GAF bound to GAS promoter elementArrowR-HSA-1031716 (Reactome)
GAS promoter region

in IFNG-regulated

genes		R-HSA-1031713 (Reactome)
GBPArrowR-HSA-1031716 (Reactome)
H2OR-HSA-877308 (Reactome)
H2OR-HSA-997326 (Reactome)
IFI30ArrowR-HSA-1031716 (Reactome)
IFN-gamma upregulated CAMsArrowR-HSA-1031716 (Reactome)
IFNG homodimerR-HSA-873926 (Reactome)
IFNG-activated factor (GAF)ArrowR-HSA-873917 (Reactome)
IFNG-activated factor (GAF)ArrowR-HSA-873927 (Reactome)
IFNG-activated factor (GAF)R-HSA-1031713 (Reactome)
IFNG-activated factor (GAF)R-HSA-873917 (Reactome)
IFNG-activated factor (GAF)R-HSA-877281 (Reactome)
IFNG-activated factor (GAF)R-HSA-997326 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:JAK2ArrowR-HSA-873926 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:JAK2ArrowR-HSA-877308 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:JAK2R-HSA-873919 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:JAK2mim-catalysisR-HSA-873919 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2:SOCS-1/-3ArrowR-HSA-877269 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2:SOCS-1/-3TBarR-HSA-873918 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2ArrowR-HSA-873919 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2R-HSA-873918 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2R-HSA-877269 (Reactome)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2mim-catalysisR-HSA-873918 (Reactome)
IFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2ArrowR-HSA-873918 (Reactome)
IFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2R-HSA-873924 (Reactome)
IFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2R-HSA-877308 (Reactome)
IFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2mim-catalysisR-HSA-873924 (Reactome)
IFNG:p-IFNGR1:p-JAK1:IFNGR2:p-JAK2ArrowR-HSA-873924 (Reactome)
IFNG:p-IFNGR1:p-JAK1:IFNGR2:p-JAK2ArrowR-HSA-873927 (Reactome)
IFNG:p-IFNGR1:p-JAK1:IFNGR2:p-JAK2R-HSA-873921 (Reactome)
IFNGR1:JAK1:INFG2:JAK2R-HSA-873926 (Reactome)
INFG induced TRIMsArrowR-HSA-1031716 (Reactome)
IRF 1-9ArrowR-HSA-1031716 (Reactome)
MHC class II alpha/beta dimerArrowR-HSA-1031716 (Reactome)
MT2AArrowR-HSA-1031716 (Reactome)
OAS proteinsArrowR-HSA-1031716 (Reactome)
PIAS1R-HSA-877281 (Reactome)
PMLArrowR-HSA-1031716 (Reactome)
PTAFRArrowR-HSA-1031716 (Reactome)
PTPN2-1mim-catalysisR-HSA-997326 (Reactome)
PTPs-SHP1/2/PTP1Bmim-catalysisR-HSA-877308 (Reactome)
PiArrowR-HSA-877308 (Reactome)
PiArrowR-HSA-997326 (Reactome)
R-HSA-1031713 (Reactome) GAF transcription factor translocated into nucleus binds to defined DNA sequence called GAS (gamma activated sequence) elements in the promoters of IFN-gamma responsive elements and initiate transcription.
R-HSA-1031716 (Reactome) IFN-gamma stimulates gene expression of about 200 genes which include the primary response genes like IRFs, Fc-gamma receptor (FCGR), GBPs (guanylate-binding proteins) and also major histocompatibility complex (MHC) class I and class II molecules, proteins involved in antigen presentation, antiviral proteins like PKR, OAS proteins etc. A wonderful list of most of the IFN-gamma inducible proteins with corresponding literature are mentioned in the review article and the supplementary document by Boehm et al 1997.
R-HSA-873917 (Reactome) Released GAF complex translocates to the nucleus and binds to the gamma-activated sequence (GAS) element present in the promoters of IFNG-regulated genes and induces the transcription of IFNG-responsive genes.
R-HSA-873918 (Reactome) The initial phosphorylation of JAK1 and JAK2 is mediated by JAK2. Autophosphorylated JAK2 may transphopshorylate JAK1 bound to IFNGR1 chain. Tyrosine 1033 in the activation loop of the JAK1 kinase domain may be the target for transphosphorylation (phosphorylation site mentioned here is based on sequence similarity with all the other JAK kinases).
R-HSA-873919 (Reactome) IFN-gamma binding to the receptor complex, induces JAK2 autophosphorylation and activation. Like all protein tyrosine kinases (PTKs) JAK2 activity also depends on the phosphorylation of tandem tyrosine residues within the activation loop that results in the removal of the activation loop from the active site. Multiple phosphorylation sites have been identified in JAK2 (tyrosines 221, 570, 868, 966, 972, 1007 and 1008 ) of which phosphorylation of tyrosine 1007 is essential for kinase activity. Tyrosine 1007 is in the activation loop and phosphorylation allows access of the catalytic loop to the ATP in the ATP binding domain. Of all the predicted phoshorylation sites only tyrosine 1007 is represented in the reaction.
R-HSA-873921 (Reactome) The phosphorylated tyrosine residue 440 in the 440YDKPH444 motif on IFNGR1 chain serves as a docking site and recruits STAT1, an SH2 domain-containing transcription factor to the functional receptor unit.
R-HSA-873922 (Reactome) STAT1 pair recruited to the receptor complex is phosphorylated near the C-terminus at residue Y701, probably by JAK2. This phosphorylation enables the STAT1 homodimer formation which is further phosphorylated on residue S727.
R-HSA-873924 (Reactome) The phosphorylated active JAK1 kinase inturn phosphorylates tyrosine residue 440 on each of the IFNGR1 chains to form two adjacent docking sites for the latent STAT1 SH2 domains.
R-HSA-873926 (Reactome) The IFNG receptor complex is a pre-assembled entity, as constitutive interactions are seen between IFNGR1 and IFNGR2, and between two IFNGR2 chains in the absence of ligand IFNG. JAK1 and JAK2 constitutively associate with the intracellular domains of the subunits of the IFNG receptor complex, providing it with tyrosine kinase activity. In unstimulated cells JAK1 preferentially associates with IFNGR1 and while JAK2 associates with IFNGR2 chains. JAK1 enhances the interaction between IFNGR1 and IFNGR2 chains, and thus has a major role in the pre-assembly of the IFNGR complex, in contrast the kinase activity of JAK2 is required to observe any signaling by IFNG.
IFNG binds directly to both the receptor chains IFNGR1 and IFNGR2. IFNGR1 is a high affinity receptor and binds directly to IFNG whereas IFNGR2 binds to IFNG in presence of IFNGR1. According to Krause et al. model IFNG binds to IFNGR1 chains first and then IFNGR2 chains interact with the IFNGR1:IFNG:IFNGR1 complex.
R-HSA-873927 (Reactome) The phosphorylated STAT1 on IFNGR1 chains homodimerize through reciprocal SH2-phosphotyrosine interactions to form p-STAT1 homodimer called gamma-activated-factor (GAF). This phosphorylated STAT1 homodimer disassociates from the receptor complex and translocates to the nucleus.
R-HSA-877269 (Reactome) SOCS-1 and SOCS-3 coprecipitates with JAK kinases upon IFNG stimulation and are able to inhibit the JAK-STAT pathway, although with different affinity and kinetics. SOCS1 and SOCS3 binds to phosphorylated JAK1/2 and prevent the tyrosine kinase activity of JAKs through their kinase inhibitory region (KIR), thereby inhibiting downstream IFNG signaling. SOCS1 may also prevent IFNG signaling by targeting the signaling machinery to ubiquitin-proteasomal degradation pathway.
R-HSA-877281 (Reactome) PIAS1 protein interacts directly with phoshorylated STAT1 dimers and inhibit the transcriptional activity of STAT1 by blocking the DNA-binding domain of STAT1. It has also been suggested that PIAS proteins might regulate transcription by promoting small ubiquitin-related modifier (SUMO1) conjugation of STAT1. The significance of STAT1 sumoylation in regulating STAT1 activity is controversial and needs to be clarified.
R-HSA-877308 (Reactome) Protein tyrosine phosphatases (PTPs) SHP1 and SHP2 down regulate the IFNG signaling by dephosphorylating the tyrosine residues critical to the activation of JAK kinases. PTP1B interacts directly with JAK2 but not JAK1 and dephosphorylate the tyrosine Y1007 on JAK2.
R-HSA-909552 (Reactome) Kinases like Protein kinase C delta (PKC-delta) and Calcium/calmodulin-dependent protein kinase II (CaMK II ) can phosphorylate STAT1 at serine 727 (S727). This phosphorylation is not required for STAT1 homodimer formation, nuclear translocation and DNA binding. However, it is essential for the full transcriptional activation of STAT1.
R-HSA-997326 (Reactome) The nuclear isoform of T cell protein tyrosine phosphatase (TC-PTP) referred as TC45 (or TC-PTPa) dephosphorylates p-STAT1 dimer in the nucleus. It can also dephosphorylate p-JAK1/3 in IFNG stimulated cells.
SOCS-1 and SOCS-3R-HSA-877269 (Reactome)
SP100ArrowR-HSA-1031716 (Reactome)
STAT1 bound to p-IFNGR1ArrowR-HSA-873921 (Reactome)
STAT1 bound to p-IFNGR1R-HSA-873922 (Reactome)
STAT1 bound to p-IFNGR1mim-catalysisR-HSA-873922 (Reactome)
STAT1-1ArrowR-HSA-997326 (Reactome)
STAT1-1R-HSA-873921 (Reactome)
SUMO1R-HSA-877281 (Reactome)
TBarR-HSA-873918 (Reactome)
p-STAT1 dimer:PIAS:SUMO1ArrowR-HSA-877281 (Reactome)
p-STAT1 dimer bound to p-IFNGR1ArrowR-HSA-909552 (Reactome)
p-STAT1 dimer bound to p-IFNGR1R-HSA-873927 (Reactome)
p-STAT1(Y701) bound to p-IFNGR1ArrowR-HSA-873922 (Reactome)
p-STAT1(Y701) bound to p-IFNGR1R-HSA-909552 (Reactome)
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