Interferon type I signaling (WP585)
Homo sapiens
The type I IFNs (IFNα family, IFNβ, IFNω, IFNε and IFNκ) all bind to and signal via the type I IFN receptor complex. The type I receptor consists of two main IFNAR1, IFNAR2c receptor chains and other accessory proteins. The pathway above (WP585) describes the Type I Interferon signaling pathways and shows both classical IFN signaling via the JAK-STAT pathway (dark lines) and other non-canonical IFN signaling pathways. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP585 CPTAC Assay Portal]
Authors
Shamith Samarajiwa , Jildau Bouwman , Kristina Hanspers , Martijn Van Iersel , Egon Willighagen , Alex Pico , and Eric WeitzActivity
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Cited In
- Understanding signaling and metabolic paths using semantified and harmonized information about biological interactions (2022).
- Hematopoietic stem-cell senescence and myocardial repair - Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 3 (2020).
- Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression (2018).
- Identification of host genomic biomarkers from multiple transcriptomics datasets for diagnosis and therapies of SARS-CoV-2 infections (2023).
- Combination of Enrichment Using Gene Ontology and Transcriptomic Analysis Revealed Contribution of Interferon Signaling to Severity of COVID-19 (2022).
- Longitudinal Neuropathological Consequences of Extracranial Radiation Therapy in Mice (2024).
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Organisms
Homo sapiensCommunities
CPTAC PancCanNetAnnotations
Pathway Ontology
immune response pathway Jak-Stat signaling pathwayLabel | Type | Compact URI | Comment |
---|---|---|---|
GTP | Metabolite | chebi:15996 | |
GDP | Metabolite | chebi:17552 | |
CRK | GeneProduct | ncbigene:1398 | |
PTPN6 | GeneProduct | ncbigene:5777 | SHP1 |
JAK1 | GeneProduct | ncbigene:3716 | |
PIAS1 | GeneProduct | ncbigene:8554 | |
FYN | GeneProduct | ncbigene:2534 | |
PTPN11 | GeneProduct | ncbigene:5781 | SHP2 |
Zap70 | GeneProduct | ncbigene:7535 | |
PTPRC | GeneProduct | ncbigene:5788 | CD45 |
PIAS3 | GeneProduct | ncbigene:10401 | |
Lck | GeneProduct | ncbigene:3932 | |
GAB2 | Protein | ncbigene:9846 | |
CBL | Protein | ncbigene:867 | |
RAPGEF1 | Protein | ncbigene:2889 | C3G |
RPS6KB1 | Protein | ncbigene:6198 | |
IFNAR2b | Protein | ncbigene:3455 | |
MAPKAP1 | Protein | ncbigene:79109 | |
CRKL | Protein | ncbigene:1399 | |
EIF4E | Protein | ncbigene:1977 | |
EIF4EBP1 | Protein | ncbigene:1978 | |
RPTOR | Protein | ncbigene:57521 | |
PDCD4 | Protein | ncbigene:27250 | |
STAT3 | Protein | ncbigene:6774 | |
IRS1 | Protein | ncbigene:3667 | |
SOCS1 | Protein | ncbigene:8651 | |
SOCS3 | Protein | ncbigene:9021 | |
IFNAR1 | Protein | ncbigene:3454 | INTERFERON RECEPTOR |
STAT1 | Protein | ncbigene:6772 | |
STAT2 | Protein | ncbigene:6773 | |
EIF4B | Protein | ncbigene:1975 | |
PIK3CD | Protein | ncbigene:5293 | |
Rac1 | Protein | ncbigene:5879 | |
MAP2K3 | Protein | ncbigene:5606 | |
STAT4 | Protein | ncbigene:6775 | |
CrkL | Protein | ncbigene:1399 | |
IRF9 | Protein | ncbigene:10379 | |
RPS6KA4 | Protein | ncbigene:8986 | |
TYK2 | Protein | ncbigene:7297 | |
FRAP1 | Protein | ncbigene:2475 | AKT |
MLST8 | Protein | ncbigene:64223 | |
EIF4A1 | Protein | ncbigene:1973 | |
REL | Protein | ncbigene:5966 | |
CREB1 | Protein | ncbigene:1385 | |
STAT5 | Protein | ncbigene:6776 | |
PRMT1 | Protein | ncbigene:3276 | |
MAP2K6 | Protein | ncbigene:5608 | |
MTOR | Protein | ncbigene:2475 | |
RAP1A | Protein | ncbigene:5906 | |
IRS2 | Protein | ncbigene:8660 | |
RPS6KA5 | Protein | ncbigene:9252 | |
PIK3R1 | Protein | ncbigene:5295 | |
VAV1 | Protein | ncbigene:7409 | |
RPS6 | Protein | ncbigene:6194 | |
MAP3K1 | Protein | ncbigene:4214 | |
GNB2L1 | Protein | ncbigene:10399 | RACK1 |
MAPK14 | Protein | ncbigene:1432 | |
IFNAR2a | Protein | ncbigene:3455 | |
IFNAR2c | Protein | ncbigene:3455 | INTERFERON RECEPTOR |
PIK3R2 | Protein | ncbigene:5296 |
References
- Soluble interferon-alpha receptor molecules are present in body fluids. Novick D, Cohen B, Rubinstein M. FEBS Lett. 1992 Dec 21;314(3):445–8. PubMed Europe PMC Scholia
- Genetic transfer of a functional human interferon alpha receptor into mouse cells: cloning and expression of its cDNA. Uzé G, Lutfalla G, Gresser I. Cell. 1990 Jan 26;60(2):225–34. PubMed Europe PMC Scholia
- Interferon-alpha engages the insulin receptor substrate-1 to associate with the phosphatidylinositol 3’-kinase. Uddin S, Yenush L, Sun XJ, Sweet ME, White MF, Platanias LC. J Biol Chem. 1995 Jul 7;270(27):15938–41. PubMed Europe PMC Scholia
- Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. Domanski P, Witte M, Kellum M, Rubinstein M, Hackett R, Pitha P, et al. J Biol Chem. 1995 Sep 15;270(37):21606–11. PubMed Europe PMC Scholia
- The human interferon alpha/beta receptor: characterization and molecular cloning. Novick D, Cohen B, Rubinstein M. Cell. 1994 May 6;77(3):391–400. PubMed Europe PMC Scholia
- The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. Müller M, Briscoe J, Laxton C, Guschin D, Ziemiecki A, Silvennoinen O, et al. Nature. 1993 Nov 11;366(6451):129–35. PubMed Europe PMC Scholia
- Identification of a novel subunit of the type I interferon receptor localized to human chromosome 21. Colamonici OR, Domanski P. J Biol Chem. 1993 May 25;268(15):10895–9. PubMed Europe PMC Scholia
- Differential regulation of the alpha/beta interferon-stimulated Jak/Stat pathway by the SH2 domain-containing tyrosine phosphatase SHPTP1. David M, Chen HE, Goelz S, Larner AC, Neel BG. Mol Cell Biol. 1995 Dec;15(12):7050–8. PubMed Europe PMC Scholia
- The type I interferon receptor mediates tyrosine phosphorylation of insulin receptor substrate 2. Platanias LC, Uddin S, Yetter A, Sun XJ, White MF. J Biol Chem. 1996 Jan 5;271(1):278–82. PubMed Europe PMC Scholia
- Molecular characterization of an alpha interferon receptor 1 subunit (IFNaR1) domain required for TYK2 binding and signal transduction. Yan H, Krishnan K, Lim JT, Contillo LG, Krolewski JJ. Mol Cell Biol. 1996 May;16(5):2074–82. PubMed Europe PMC Scholia
- Interaction of the c-cbl proto-oncogene product with the Tyk-2 protein tyrosine kinase. Uddin S, Gardziola C, Dangat A, Yi T, Platanias LC. Biochem Biophys Res Commun. 1996 Aug 23;225(3):833–8. PubMed Europe PMC Scholia
- Interaction of p59fyn with interferon-activated Jak kinases. Uddin S, Sher DA, Alsayed Y, Pons S, Colamonici OR, Fish EN, et al. Biochem Biophys Res Commun. 1997 Jun 9;235(1):83–8. PubMed Europe PMC Scholia
- Cloning and characterization of soluble and transmembrane isoforms of a novel component of the murine type I interferon receptor, IFNAR 2. Owczarek CM, Hwang SY, Holland KA, Gulluyan LM, Tavaria M, Weaver B, et al. J Biol Chem. 1997 Sep 19;272(38):23865–70. PubMed Europe PMC Scholia
- Janus kinase-dependent activation of insulin receptor substrate 1 in response to interleukin-4, oncostatin M, and the interferons. Burfoot MS, Rogers NC, Watling D, Smith JM, Pons S, Paonessaw G, et al. J Biol Chem. 1997 Sep 26;272(39):24183–90. PubMed Europe PMC Scholia
- The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein. Ahmad S, Alsayed YM, Druker BJ, Platanias LC. J Biol Chem. 1997 Nov 28;272(48):29991–4. PubMed Europe PMC Scholia
- Inhibition of Stat1-mediated gene activation by PIAS1. Liu B, Liao J, Rao X, Kushner SA, Chung CD, Chang DD, et al. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10626–31. PubMed Europe PMC Scholia
- The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities. Song MM, Shuai K. J Biol Chem. 1998 Dec 25;273(52):35056–62. PubMed Europe PMC Scholia
- Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway. You M, Yu DH, Feng GS. Mol Cell Biol. 1999 Mar;19(3):2416–24. PubMed Europe PMC Scholia
- CrkL and CrkII participate in the generation of the growth inhibitory effects of interferons on primary hematopoietic progenitors. Platanias LC, Uddin S, Bruno E, Korkmaz M, Ahmad S, Alsayed Y, et al. Exp Hematol. 1999 Aug;27(8):1315–21. PubMed Europe PMC Scholia
- Recruitment of Stat4 to the human interferon-alpha/beta receptor requires activated Stat2. Farrar JD, Smith JD, Murphy TL, Murphy KM. J Biol Chem. 2000 Jan 28;275(4):2693–7. PubMed Europe PMC Scholia
- Involvement of the Gab2 scaffolding adapter in type I interferon signalling. Baychelier F, Nardeux PC, Cajean-Feroldi C, Ermonval M, Guymarho J, Tovey MG, et al. Cell Signal. 2007 Oct;19(10):2080–7. PubMed Europe PMC Scholia
- Soluble IFN receptor potentiates in vivo type I IFN signaling and exacerbates TLR4-mediated septic shock. Samarajiwa SA, Mangan NE, Hardy MP, Najdovska M, Dubach D, Braniff SJ, et al. J Immunol. 2014 May 1;192(9):4425–35. PubMed Europe PMC Scholia