Type II Interferon Signaling Pathways

Click on one of the buttons below to see the signaling pathways that are activated by members of either the type I or type III interferon families.

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Type II IFN
Type II IFN
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IFN-gamma R2
IFN-gamma R2
IFN-gamma R1/CD119
IFN-gamma R1/CD119
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Jak2
Jak2
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Jak1
Jak1
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Jak2
Jak2
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IRS1/2
IRS1/2
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PI 3-K
PI 3-K
Akt
Akt
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IKK-beta
IKK-beta
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I kappa B
I kappa B
NF-kappa B
NF-kappa B
I kappa B
I kappa B
Proteasome
Proteasome
NF-kappa B
NF-kappa B
Survival Signals
Survival Signals
Expression of Antigen
Processing/Presentation Signals
Expression of Antigen
Processing/Presentation Signals
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TSC1/2
TSC1/2
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mTOR
mTOR
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4EBP1
4EBP1
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eIF4E
eIF4E
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eIF4E
eIF4E
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4EBP1
4EBP1
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p70 S6 Kinase
p70 S6 Kinase
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RPS6
RPS6
mRNA Translation
mRNA Translation

Proteolytic Processing

Proteolytic Processing

PI 3-K
PI 3-K
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PKC delta
PKC delta
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STAT1
STAT1
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STAT1
STAT1
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STAT1
STAT1
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STAT1 Dimer
STAT1 Dimer
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Regulation of the
Inflammatory Response
Regulation of the
Inflammatory Response
MEK1/2
MEK1/2
ERK1/2
ERK1/2
C/EBP
C/EBP
p38
p38

Autophagy

Autophagy

Endoplasmic reticulum
Endoplasmic reticulum

Proteolytic
Processing

Proteolytic
Processing

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ATF6
ATF6
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Golgi apparatus
Golgi apparatus
ATF6
ATF6
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Additional Target Genes
Additional Target Genes

GAS

GAS

Overview of Type II Interferon Signaling Pathways

IFN-gamma is the only type II interferon. While it does not share structural homology or a common receptor with the type I IFNs, it too has antiviral and immunomodulatory properties. The biologically active form of IFN-gamma is a noncovalently-linked homodimer. This homodimer binds to the extracellular domain of two IFN-gamma R1/CD119 chains, which interact with IFN-gamma R2 to form the functional IFN-gamma receptor complex. The IFN-gamma R1 subunits of the receptor complex are associated with Jak1, while the IFN-gamma R2 subunits are associated with Jak2. Activation of Jak1 and Jak2 results in phosphorylation of the receptor and subsequent recruitment and phosphorylation of STAT1. STAT1 phosphorylation leads to its homodimerization and nuclear translocation. Once in the nucleus, STAT1 homodimers bind to IFN-gamma-activated sequence (GAS) elements in the promoters of target genes to regulate their transcription. Many of the target genes that are induced by IFN-gamma/STAT1 signaling are transcription factors that then drive the expression of secondary response genes. In addition, IFN-gamma signaling can activate MAPK, PI 3-K-Akt, and NF-kappa B signaling pathways to regulate the expression of a number of other genes. IFN-gamma signaling plays a key role in host defense by promoting macrophage activation, upregulating the expression of antigen processing and presentation molecules, driving the development and activation of Th1 cells, enhancing natural killer cell activity, regulating B cell functions, and inducing the production of chemokines that promote effector cell trafficking to sites of inflammation. While IFN-gamma has historically been known for its cytotoxic, cytostatic, and anti-tumor properties, multiple studies have also suggested that IFN-gamma may also have context-dependent proliferative and pro-tumorigenic effects.

To learn more, please visit our IL-10/Interferon Family Research Area page

Type II Interferon Signaling Pathways background image 1