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 Weitz

Activity

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Cited In

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Organisms

Homo sapiens

Communities

CPTAC PancCanNet

Annotations

Pathway Ontology

immune response pathway Jak-Stat signaling pathway

Participants

Label 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
STAT4 Protein ncbigene:6775
TYK2 Protein ncbigene:7297
FRAP1 Protein ncbigene:2475 AKT
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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
STAT2 Protein ncbigene:6773
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
STAT1 Protein ncbigene:6772
STAT1 Protein ncbigene:6772
IFNAR2c Protein ncbigene:3455 INTERFERON RECEPTOR
STAT3 Protein ncbigene:6774
Rac1 Protein ncbigene:5879
PIK3R2 Protein ncbigene:5296
STAT1 Protein ncbigene:6772
STAT3 Protein ncbigene:6774
STAT3 Protein ncbigene:6774
STAT1 Protein ncbigene:6772
STAT2 Protein ncbigene:6773

References

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  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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