Type I Interferon Signaling Pathways

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

Type I IFN
Type I IFN
IFN-alpha/beta R1
IFN-alpha/beta R1
IFN-alpha/beta R2
IFN-alpha/beta R2
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Tyk2
Tyk2
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Jak1
Jak1
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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
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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
RPS6
RPS6
mRNA Translation
mRNA Translation

Protein Synthesis

Protein Synthesis

Survival Signals
Survival Signals
Expression of Antigen
Processing/Presentation Signals
Expression of Antigen
Processing/Presentation Signals
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Vav
Vav
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GEFs
GEFs
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Rac1
Rac1
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MAPKKK
MAPKKK
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MKK3
MKK3
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MKK6
MKK6
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p38
p38
MNK1/2
MNK1/2
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MAPKAPK2/3
MAPKAPK2/3
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MSK1/2
MSK1/2
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CREB
CREB
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Histone H3
Histone H3
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Growth
Inhibition

Growth
Inhibition

Chromatin Remodeling
Chromatin Remodeling
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STAT1
STAT1
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STAT1
STAT1
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STAT2
STAT2
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IRF9
IRF9
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STAT1
STAT1
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STAT2
STAT2
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IRF9
IRF9
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ISGF3
ISGF3
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STAT1
STAT1
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STAT2
STAT2
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IRF9
IRF9
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IFN-Stimulated Genes
IFN-Stimulated Genes
Anti-Viral Response
Anti-Viral Response
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STAT1
STAT1
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STAT1
STAT1
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STAT3
STAT3
Homo-/
Heterodimers
Homo-/
Heterodimers
STAT Dimer
or CrkL-STAT5
STAT Dimer
or CrkL-STAT5
Regulation of the
Inflammatory Response
Regulation of the
Inflammatory Response
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CrkL
CrkL
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STAT5
STAT5
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STAT2
STAT2
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STAT4
STAT4
STAT5
STAT5
STAT6
STAT6

ISRE

ISRE

GAS

GAS

Overview of Type I Interferon Signaling Pathways

Type I IFNs are produced following recognition of microbial products by cell surface and intracellular pattern recognition receptors. The type I interferon (IFN) family consists of multiple IFN-alpha subtypes, IFN-beta, IFN-delta, IFN-epsilon, IFN-kappa, IFN-tau, IFN-omega, and IFN-zeta/Limitin. IFN-alpha, IFN-beta, IFN-epsilon, IFN-kappa, and IFN-omega are all found in humans, while IFN-delta, IFN-tau, and IFN-zeta have only been described in pigs, cattle, and mice, respectively. No human homologues of these three type I interferon subclasses have been identified. All type I interferons have significant structural homology and bind to a common heterodimeric receptor consisting of the IFN-alpha/beta RI and IFN-alpha/beta R2 subunits, which are expressed on most cell types. Receptor engagement activates the IFN-alpha/beta R1-associated Tyk2 protein tyrosine kinase and the IFN-alpha/beta R2-associated Jak1 protein tyrosine kinase. These kinases subsequently regulate the phosphorylation and activation of different STAT proteins. Activated STAT proteins homo- or heterodimerize and translocate to the nucleus, where they promote the expression of numerous target genes. In addition, type I IFNs activate the MAPK, PI 3-K-Akt, and NF-kappa B signaling pathways. One transcriptional complex that is formed following stimulation by type I IFNs is the IFN-stimulated gene factor 3 (ISGF3) complex. This complex consists of phosphorylated STAT1, STAT2, and IRF9 and binds to IFN-stimulated response elements (ISREs) found in the promoters of numerous IFN-stimulated genes (ISGs). Other STAT homo- or heterodimers induced by type I IFNs bind to regulatory sequences in the promoters of target genes known as IFN-gamma-activated sequence (GAS) sites. Binding of STAT proteins to either ISREs or GAS sites regulates the expression of several hundred ISGs, which mediate the anti-viral, anti-proliferative, and apoptotic effects of type I IFNs.

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

Type I Interferon Signaling Pathways background image 1