Interferon gamma signaling (Homo sapiens)

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1-428-3020, 25-2737, 3828, 30, 3141-442039, 4016-1932, 3334-366, 7, 10-158, 9, 44-4821, 2223-25lysosomal lumennucleoplasmcytosolendoplasmic reticulum lumenIFNG-activated factor (GAF)IFNG homodimerH2OATPSP100H2OPTPs-SHP1/2/PTP1BADPIFNG:IFNGR1:JAK1:IFNGR2:JAK2TC-PTPaADPGBPOAS proteinsGAF bound to GAS promoter elementATPp-STAT1(Y701) bound to p-IFNGR1ADPADPHLA IIPTP1BClass I MHC heavy chain (MHC HC)STAT1SUMO1IFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2ATPGAS promoter region in IFNG-regulated genesIFNG:IFNGR1:JAK1:IFNGR2:p-JAK2:SOCS-1/-3PMLPAF receptorATPIFN-gamma upregulated CAMsSHP1STAT1-alphaSTAT1 bound to p-IFNGR1IFNG:p-IFNGR1:p-JAK1:IFNGR2:p-JAK2IFNGR1:JAK1:INFG2:JAK2ATPIFNG:IFNGR1:JAK1:IFNGR2:p-JAK2SOCS-1 and SOCS-3FCGRGamma-interferon-inducible lysosomal thiol reductaseCaMKII and PKC-deltaPIAS1Metallothionein-2ADPOrthophosphateBeta-2-microglobulinp-STAT1 dimer bound to p-IFNGR1p-STAT1 dimer:PIAS:SUMO1MHC class II transactivatorIFNG-activated factor (GAF)OrthophosphateIRF 1-956, 78, 9


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.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
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
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Beta-2-

microglobulin

ProteinP61769 (UniProt)
CaMKII and PKC-delta ProteinREACT_26704 (Reactome)
Class I MHC

heavy chain (MHC HC)

ProteinREACT_26784 (Reactome)
FCGR ProteinREACT_26475 (Reactome)
GAF bound to GAS

promoter element

ComplexREACT_25470 (Reactome)
GAS promoter region

in IFNG-regulated genes

UnknownREACT_26763 (Reactome)
GBP ProteinREACT_26189 (Reactome)
Gamma-interferon-

inducible lysosomal thiol reductase

ProteinP13284 (UniProt)
H2O Metabolite15377 (ChEBI)
HLA II ProteinREACT_13194 (Reactome)
IFN-gamma

upregulated CAMs

ProteinREACT_26072 (Reactome)
IFNG homodimer ComplexREACT_26955 (Reactome)
IFNG-activated

factor (GAF)

ComplexREACT_26144 (Reactome)
IFNG-activated

factor (GAF)

ComplexREACT_26637 (Reactome)
IFNG:IFNGR1:JAK1:

IFNGR2:JAK2

ComplexREACT_25865 (Reactome)
IFNG:IFNGR1:JAK1:

IFNGR2:p-JAK2

ComplexREACT_26738 (Reactome)
IFNG:IFNGR1:JAK1:

IFNGR2:p-JAK2: SOCS-1/-3

ComplexREACT_26775 (Reactome)
IFNG:IFNGR1:p-

JAK1:IFNGR2:p- JAK2

ComplexREACT_26286 (Reactome)
IFNG:p-IFNGR1:p-

JAK1:IFNGR2:p- JAK2

ComplexREACT_25650 (Reactome)
IFNGR1:JAK1:

INFG2:JAK2

ComplexREACT_25803 (Reactome)
IRF 1-9 ProteinREACT_26465 (Reactome)
MHC class II

transactivator

ProteinP33076 (UniProt)
Metallothionein-2 ProteinP02795 (UniProt)
OAS proteins ProteinREACT_26755 (Reactome)
Orthophosphate Metabolite18367 (ChEBI)
PAF receptor ProteinP25105 (UniProt)
PIAS1 ProteinO75925 (UniProt)
PML ProteinP29590 (UniProt)
PTP1B ProteinP18031 (UniProt)
PTPs-

SHP1/2/PTP1B

ProteinREACT_26675 (Reactome)
SHP1 ProteinP29350 (UniProt)
SOCS-1 and

SOCS-3

ProteinREACT_25587 (Reactome)
SP100 ProteinP23497 (UniProt)
STAT1 ProteinP42224-1 (UniProt)
STAT1 bound to p-

IFNGR1

ComplexREACT_26587 (Reactome)
STAT1-alpha ProteinP42224-1 (UniProt)
SUMO1 ProteinP63165 (UniProt)
TC-PTPa ProteinP17706-2 (UniProt)
p-STAT1 dimer

bound to p-IFNGR1

ComplexREACT_25936 (Reactome)
p-STAT1 dimer:

PIAS:SUMO1

ComplexREACT_25840 (Reactome)
p-STAT1(Y701)

bound to p-IFNGR1

ComplexREACT_26108 (Reactome)

Annotated Interactions

No annotated interactions

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