Interferon gamma signaling (Homo sapiens)

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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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History

CompareRevisionActionTimeUserComment
44865view09:58, 6 October 2011MartijnVanIerselOntology Term : 'immune response pathway' added !
42056view21:53, 4 March 2011MaintBotAutomatic update
39862view05:53, 21 January 2011MaintBotNew pathway

External references

View all...
NameTypeDatabase referenceComment
FCGR ProteinREACT_26475 (Reactome)
IFNGR1:JAK1:

INFG2:JAK2

ComplexREACT_25803 (Reactome)
Orthophosphate Metabolite18367 (ChEBI)
IFNG:IFNGR1:JAK1:

IFNGR2:JAK2

ComplexREACT_25865 (Reactome)
IRF 1-9 ProteinREACT_26465 (Reactome)
ATP Metabolite15422 (ChEBI)
GAS promoter region

in IFNG-regulated genes

UnknownREACT_26763 (Reactome)
IFNG:IFNGR1:JAK1:

IFNGR2:p-JAK2

ComplexREACT_26738 (Reactome)
PML ProteinP29590 (UniProt)
ADP Metabolite16761 (ChEBI)
IFNG homodimer ComplexREACT_26955 (Reactome)
IFNG:IFNGR1:p-

JAK1:IFNGR2:p- JAK2

ComplexREACT_26286 (Reactome)
STAT1 ProteinP42224-1 (UniProt)
IFNG:p-IFNGR1:p-

JAK1:IFNGR2:p- JAK2

ComplexREACT_25650 (Reactome)
GBP ProteinREACT_26189 (Reactome)
STAT1-alpha ProteinP42224-1 (UniProt)
PAF receptor ProteinP25105 (UniProt)
STAT1 bound to p-

IFNGR1

ComplexREACT_26587 (Reactome)
IFN-gamma

upregulated CAMs

ProteinREACT_26072 (Reactome)
p-STAT1(Y701)

bound to p-IFNGR1

ComplexREACT_26108 (Reactome)
Gamma-interferon-

inducible lysosomal thiol reductase

ProteinP13284 (UniProt)
IFNG-activated

factor (GAF)

ComplexREACT_26637 (Reactome)
H2O Metabolite15377 (ChEBI)
IFNG-activated

factor (GAF)

ComplexREACT_26144 (Reactome)
PTPs-

SHP1/2/PTP1B

ProteinREACT_26675 (Reactome)
IFNG:IFNGR1:JAK1:

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

ComplexREACT_26775 (Reactome)
TC-PTPa ProteinP17706-2 (UniProt)
SOCS-1 and

SOCS-3

ProteinREACT_25587 (Reactome)
GAF bound to GAS

promoter element

ComplexREACT_25470 (Reactome)
SHP1 ProteinP29350 (UniProt)
MHC class II

transactivator

ProteinP33076 (UniProt)
PIAS1 ProteinO75925 (UniProt)
Class I MHC

heavy chain (MHC HC)

ProteinREACT_26784 (Reactome)
SUMO1 ProteinP63165 (UniProt)
Metallothionein-2 ProteinP02795 (UniProt)
p-STAT1 dimer:

PIAS:SUMO1

ComplexREACT_25840 (Reactome)
OAS proteins ProteinREACT_26755 (Reactome)
p-STAT1 dimer

bound to p-IFNGR1

ComplexREACT_25936 (Reactome)
Beta-2-

microglobulin

ProteinP61769 (UniProt)
CaMKII and PKC-delta ProteinREACT_26704 (Reactome)
SP100 ProteinP23497 (UniProt)
PTP1B ProteinP18031 (UniProt)
HLA II ProteinREACT_13194 (Reactome)
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