Interferon type I signaling pathways (WP3213)

Bos taurus

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.

Authors

Martina Summer-Kutmon and Egon Willighagen

Activity

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

Jak-Stat signaling pathway immune response pathway

Participants

Label Type Compact URI Comment
GTP Metabolite chebi:15996
GDP Metabolite chebi:17552
CRK GeneProduct ensembl:ENSBTAG00000005665 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1398
PTPN6 GeneProduct ensembl:ENSBTAG00000020294 SHP1
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5777
JAK1 GeneProduct ensembl:ENSBTAG00000003147 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
PIAS1 GeneProduct ensembl:ENSBTAG00000005564 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8554
FYN GeneProduct ensembl:ENSBTAG00000011851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
PTPN11 GeneProduct ensembl:ENSBTAG00000002048 SHP2
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
ZAP70 GeneProduct ensembl:ENSBTAG00000005892 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7535
PTPRC GeneProduct ensembl:ENSBTAG00000023144 CD45
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5788
PIAS3 GeneProduct ensembl:ENSBTAG00000021634 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10401
LCK GeneProduct ensembl:ENSBTAG00000012695 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3932
CBL Protein ensembl:ENSBTAG00000006817 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:867
RAPGEF1 Protein ensembl:ENSBTAG00000020791 C3G
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2889
RPS6KB1 Protein ensembl:ENSBTAG00000016851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
IFNAR2 Protein ensembl:ENSBTAG00000015212 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3455
MAPKAP1 Protein ensembl:ENSBTAG00000010271 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:79109
CRKL Protein ensembl:ENSBTAG00000045548 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1399
EIF4E Protein ensembl:ENSBTAG00000009522 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1977
EIF4EBP1 Protein ensembl:ENSBTAG00000027654 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1978
RPTOR Protein ensembl:ENSBTAG00000002883 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:57521
PDCD4 Protein ensembl:ENSBTAG00000019434 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:27250
STAT3 Protein ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
IRS1 Protein ensembl:ENSBTAG00000021308 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3667
SOCS1 Protein ensembl:ENSBTAG00000004386 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8651
SOCS3 Protein ensembl:ENSBTAG00000008441 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
IFNAR1 Protein ensembl:ENSBTAG00000021819 INTERFERON RECEPTOR
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3454
STAT1 Protein ensembl:ENSBTAG00000007867 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
STAT2 Protein ensembl:ENSBTAG00000004380 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6773
EIF4B Protein ensembl:ENSBTAG00000006883 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1975
PIK3CD Protein ensembl:ENSBTAG00000018984 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5293
RAC1 Protein ensembl:ENSBTAG00000009233 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
MAP2K3 Protein ensembl:ENSBTAG00000010576 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5606
STAT4 Protein ensembl:ENSBTAG00000046699 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6775
RPS6KA4 Protein ensembl:ENSBTAG00000039153 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8986
TYK2 Protein ensembl:ENSBTAG00000011698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297
MTOR Protein ensembl:ENSBTAG00000015325 AKT
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2475
MLST8 Protein ensembl:ENSBTAG00000009928 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:64223
EIF4A1 Protein ensembl:ENSBTAG00000000132 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1973
REL Protein ensembl:ENSBTAG00000015386 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5966
CREB1 Protein ensembl:ENSBTAG00000005474 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
STAT5A Protein ensembl:ENSBTAG00000009496 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6776
PRMT1 Protein ensembl:ENSBTAG00000001357 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3276
MAP2K6 Protein ensembl:ENSBTAG00000001609 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5608
MTOR Protein ensembl:ENSBTAG00000015325 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2475
RAP1A Protein ensembl:ENSBTAG00000014710 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5906
IRS2 Protein ensembl:ENSBTAG00000012019 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8660
RPS6KA5 Protein ensembl:ENSBTAG00000010906 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9252
PIK3R1 Protein ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
VAV1 Protein ensembl:ENSBTAG00000039160 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7409
RPS6 Protein ensembl:ENSBTAG00000014449 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6194
MAP3K1 Protein ensembl:ENSBTAG00000013790 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4214
GNB2L1 Protein ensembl:ENSBTAG00000019648 RACK1
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10399
MAPK14 Protein ensembl:ENSBTAG00000020783 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
IFNAR2 Protein ensembl:ENSBTAG00000015212 INTERFERON RECEPTOR
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3455

References

  1. Tyrosine phosphorylation is required for activation of an alpha interferon-stimulated transcription factor. Gutch MJ, Daly C, Reich NC. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11411–5. PubMed Europe PMC Scholia
  2. 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
  3. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Schindler C, Shuai K, Prezioso VR, Darnell JE Jr. Science. 1992 Aug 7;257(5071):809–13. PubMed Europe PMC Scholia
  4. A transcription factor with SH2 and SH3 domains is directly activated by an interferon alpha-induced cytoplasmic protein tyrosine kinase(s). Fu XY. Cell. 1992 Jul 24;70(2):323–35. PubMed Europe PMC Scholia
  5. 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
  6. 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
  7. 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
  8. Activation of JAK kinases and STAT proteins by interleukin-2 and interferon alpha, but not the T cell antigen receptor, in human T lymphocytes. Beadling C, Guschin D, Witthuhn BA, Ziemiecki A, Ihle JN, Kerr IM, et al. EMBO J. 1994 Dec 1;13(23):5605–15. PubMed Europe PMC Scholia
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. STATs and gene regulation. Darnell JE Jr. Science. 1997 Sep 12;277(5332):1630–5. PubMed Europe PMC Scholia
  18. 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
  19. 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
  20. The IRS-pathway operates distinctively from the Stat-pathway in hematopoietic cells and transduces common and distinct signals during engagement of the insulin or interferon-alpha receptors. Uddin S, Fish EN, Sher D, Gardziola C, Colamonici OR, Kellum M, et al. Blood. 1997 Oct 1;90(7):2574–82. PubMed Europe PMC Scholia
  21. 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
  22. 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
  23. 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
  24. Activation of a CrkL-stat5 signaling complex by type I interferons. Fish EN, Uddin S, Korkmaz M, Majchrzak B, Druker BJ, Platanias LC. J Biol Chem. 1999 Jan 8;274(2):571–3. PubMed Europe PMC Scholia
  25. 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
  26. 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
  27. Activation of the p38 mitogen-activated protein kinase by type I interferons. Uddin S, Majchrzak B, Woodson J, Arunkumar P, Alsayed Y, Pine R, et al. J Biol Chem. 1999 Oct 15;274(42):30127–31. PubMed Europe PMC Scholia
  28. 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
  29. 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
  30. 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