Interferon type I signaling pathways (Bos taurus)

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16CREBTRANSLATION INITIATIONGASType I IFNsISRE1, 8, 19-211813GAF complexNegative regulators of IFN transcriptionInterferon Stimulated Response ElementmTORC1Negative regulators of IFN signalingISGF3 complexType I IFN Receptor ComplexPI3K complexGamma Activated SequenceRAPGEF1IFNAR2SOCS3STAT4RELEIF4BCBLFYNMLST8CRKLIRS2RPS6KA5EIF4A1MTORGTPSTAT4PIAS3ZAP70PTPRCPDCD4PIAS1GAB2RPTORMTORMAPKAP1RPS6KB1LCKPRMT1MAP2K6STAT1RAC1TYK2STAT1SOCS1IRF9CREB1STAT3STAT5AGNB2L1IRS1EIF4EBP1PIK3CDSTAT1STAT2CRKVAV1PTPN11CRKLMAPK14IFNAR2RPS6KA4PTPN6IFNAR2MAP2K3IFNAR1RAP1AJAK1RPS6MAP3K1STAT2GDPEIF4EPIK3R126225, 2510, 23, 27241791231614729, 30, 32152, 28103STAT3RAC1PPPPPPPPPPPPPIK3R2PPPPNFkBSTAT1STAT3STAT3STAT1STAT2PPPPPPPTrans-Signalling


Description

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.

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HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP585(80201) with a 95.0% conversion rate.

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Bibliography

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  1. Fu XY; ''A transcription factor with SH2 and SH3 domains is directly activated by an interferon alpha-induced cytoplasmic protein tyrosine kinase(s).''; Cell, 1992 PubMed Europe PMC Scholia
  2. You M, Yu DH, Feng GS; ''Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway.''; Mol Cell Biol, 1999 PubMed Europe PMC Scholia
  3. Uzé G, Lutfalla G, Gresser I; ''Genetic transfer of a functional human interferon alpha receptor into mouse cells: cloning and expression of its cDNA.''; Cell, 1990 PubMed Europe PMC Scholia
  4. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H; ''MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer.''; Oncogene, 2008 PubMed Europe PMC Scholia
  5. Müller M, Briscoe J, Laxton C, Guschin D, Ziemiecki A, Silvennoinen O, Harpur AG, Barbieri G, Witthuhn BA, Schindler C; ''The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction.''; Nature, 1993 PubMed Europe PMC Scholia
  6. Baychelier F, Nardeux PC, Cajean-Feroldi C, Ermonval M, Guymarho J, Tovey MG, Eid P; ''Involvement of the Gab2 scaffolding adapter in type I interferon signalling.''; Cell Signal, 2007 PubMed Europe PMC Scholia
  7. Song MM, Shuai K; ''The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities.''; J Biol Chem, 1998 PubMed Europe PMC Scholia
  8. Darnell JE Jr; ''STATs and gene regulation.''; Science, 1997 PubMed Europe PMC Scholia
  9. Liu B, Liao J, Rao X, Kushner SA, Chung CD, Chang DD, Shuai K; ''Inhibition of Stat1-mediated gene activation by PIAS1.''; Proc Natl Acad Sci U S A, 1998 PubMed Europe PMC Scholia
  10. Domanski P, Witte M, Kellum M, Rubinstein M, Hackett R, Pitha P, Colamonici OR; ''Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling.''; J Biol Chem, 1995 PubMed Europe PMC Scholia
  11. Liu X, Zhang Z, Sun L, Chai N, Tang S, Jin J, Hu H, Nie Y, Wang X, Wu K, Jin H, Fan D; ''MicroRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4.''; Carcinogenesis, 2011 PubMed Europe PMC Scholia
  12. Ahmad S, Alsayed YM, Druker BJ, Platanias LC; ''The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein.''; J Biol Chem, 1997 PubMed Europe PMC Scholia
  13. Uddin S, Fish EN, Sher D, Gardziola C, Colamonici OR, Kellum M, Pitha PM, White MF, Platanias LC; ''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.''; Blood, 1997 PubMed Europe PMC Scholia
  14. Uddin S, Gardziola C, Dangat A, Yi T, Platanias LC; ''Interaction of the c-cbl proto-oncogene product with the Tyk-2 protein tyrosine kinase.''; Biochem Biophys Res Commun, 1996 PubMed Europe PMC Scholia
  15. Farrar JD, Smith JD, Murphy TL, Murphy KM; ''Recruitment of Stat4 to the human interferon-alpha/beta receptor requires activated Stat2.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
  16. Uddin S, Majchrzak B, Woodson J, Arunkumar P, Alsayed Y, Pine R, Young PR, Fish EN, Platanias LC; ''Activation of the p38 mitogen-activated protein kinase by type I interferons.''; J Biol Chem, 1999 PubMed Europe PMC Scholia
  17. Platanias LC, Uddin S, Yetter A, Sun XJ, White MF; ''The type I interferon receptor mediates tyrosine phosphorylation of insulin receptor substrate 2.''; J Biol Chem, 1996 PubMed Europe PMC Scholia
  18. Fish EN, Uddin S, Korkmaz M, Majchrzak B, Druker BJ, Platanias LC; ''Activation of a CrkL-stat5 signaling complex by type I interferons.''; J Biol Chem, 1999 PubMed Europe PMC Scholia
  19. Gutch MJ, Daly C, Reich NC; ''Tyrosine phosphorylation is required for activation of an alpha interferon-stimulated transcription factor.''; Proc Natl Acad Sci U S A, 1992 PubMed Europe PMC Scholia
  20. Beadling C, Guschin D, Witthuhn BA, Ziemiecki A, Ihle JN, Kerr IM, Cantrell DA; ''Activation of JAK kinases and STAT proteins by interleukin-2 and interferon alpha, but not the T cell antigen receptor, in human T lymphocytes.''; EMBO J, 1994 PubMed Europe PMC Scholia
  21. Schindler C, Shuai K, Prezioso VR, Darnell JE Jr; ''Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor.''; Science, 1992 PubMed Europe PMC Scholia
  22. Yan H, Krishnan K, Lim JT, Contillo LG, Krolewski JJ; ''Molecular characterization of an alpha interferon receptor 1 subunit (IFNaR1) domain required for TYK2 binding and signal transduction.''; Mol Cell Biol, 1996 PubMed Europe PMC Scholia
  23. Novick D, Cohen B, Rubinstein M; ''The human interferon alpha/beta receptor: characterization and molecular cloning.''; Cell, 1994 PubMed Europe PMC Scholia
  24. Uddin S, Sher DA, Alsayed Y, Pons S, Colamonici OR, Fish EN, White MF, Platanias LC; ''Interaction of p59fyn with interferon-activated Jak kinases.''; Biochem Biophys Res Commun, 1997 PubMed Europe PMC Scholia
  25. Burfoot MS, Rogers NC, Watling D, Smith JM, Pons S, Paonessaw G, Pellegrini S, White MF, Kerr IM; ''Janus kinase-dependent activation of insulin receptor substrate 1 in response to interleukin-4, oncostatin M, and the interferons.''; J Biol Chem, 1997 PubMed Europe PMC Scholia
  26. Platanias LC, Uddin S, Bruno E, Korkmaz M, Ahmad S, Alsayed Y, Van Den Berg D, Druker BJ, Wickrema A, Hoffman R; ''CrkL and CrkII participate in the generation of the growth inhibitory effects of interferons on primary hematopoietic progenitors.''; Exp Hematol, 1999 PubMed Europe PMC Scholia
  27. Colamonici OR, Domanski P; ''Identification of a novel subunit of the type I interferon receptor localized to human chromosome 21.''; J Biol Chem, 1993 PubMed Europe PMC Scholia
  28. David M, Chen HE, Goelz S, Larner AC, Neel BG; ''Differential regulation of the alpha/beta interferon-stimulated Jak/Stat pathway by the SH2 domain-containing tyrosine phosphatase SHPTP1.''; Mol Cell Biol, 1995 PubMed Europe PMC Scholia
  29. Owczarek CM, Hwang SY, Holland KA, Gulluyan LM, Tavaria M, Weaver B, Reich NC, Kola I, Hertzog PJ; ''Cloning and characterization of soluble and transmembrane isoforms of a novel component of the murine type I interferon receptor, IFNAR 2.''; J Biol Chem, 1997 PubMed Europe PMC Scholia
  30. Novick D, Cohen B, Rubinstein M; ''Soluble interferon-alpha receptor molecules are present in body fluids.''; FEBS Lett, 1992 PubMed Europe PMC Scholia
  31. Uddin S, Yenush L, Sun XJ, Sweet ME, White MF, Platanias LC; ''Interferon-alpha engages the insulin receptor substrate-1 to associate with the phosphatidylinositol 3'-kinase.''; J Biol Chem, 1995 PubMed Europe PMC Scholia
  32. Samarajiwa SA, Mangan NE, Hardy MP, Najdovska M, Dubach D, Braniff SJ, Owczarek CM, Hertzog PJ; ''Soluble IFN receptor potentiates in vivo type I IFN signaling and exacerbates TLR4-mediated septic shock.''; J Immunol, 2014 PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
107069view14:15, 17 September 2019MaintBotChEBI identifier normalization
85346view10:14, 9 May 2016EgonwReplaced a mim-conversion with Arrow.
80811view15:27, 30 June 2015MkutmonNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
CBLProteinENSBTAG00000006817 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:867
CREB1ProteinENSBTAG00000005474 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
CRKGeneProductENSBTAG00000005665 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1398
CRKLProteinENSBTAG00000045548 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1399
EIF4A1ProteinENSBTAG00000000132 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1973
EIF4BProteinENSBTAG00000006883 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1975
EIF4EBP1ProteinENSBTAG00000027654 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1978
EIF4EProteinENSBTAG00000009522 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1977
FYNGeneProductENSBTAG00000011851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
GAB2Protein
GDPMetaboliteCHEBI:17552 (ChEBI)
GNB2L1ProteinENSBTAG00000019648 (Ensembl)
  • RACK1
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10399
GTPMetaboliteCHEBI:15996 (ChEBI)
IFNAR1ProteinENSBTAG00000021819 (Ensembl)
  • INTERFERON RECEPTOR
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3454
IFNAR2ProteinENSBTAG00000015212 (Ensembl)
  • INTERFERON RECEPTOR
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3455
IRF9ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000005816;En:ENSBTAG00000005815;
IRS1ProteinENSBTAG00000021308 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3667
IRS2ProteinENSBTAG00000012019 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8660
JAK1GeneProductENSBTAG00000003147 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
LCKGeneProductENSBTAG00000012695 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3932
MAP2K3ProteinENSBTAG00000010576 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5606
MAP2K6ProteinENSBTAG00000001609 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5608
MAP3K1ProteinENSBTAG00000013790 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4214
MAPK14ProteinENSBTAG00000020783 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
MAPKAP1ProteinENSBTAG00000010271 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:79109
MLST8ProteinENSBTAG00000009928 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:64223
MTORProteinENSBTAG00000015325 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2475
PDCD4ProteinENSBTAG00000019434 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:27250
PIAS1GeneProductENSBTAG00000005564 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8554
PIAS3GeneProductENSBTAG00000021634 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10401
PIK3CDProteinENSBTAG00000018984 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5293
PIK3R1ProteinENSBTAG00000010989 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PIK3R2ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000002350;En:ENSBTAG00000002350;
PRMT1ProteinENSBTAG00000001357 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3276
PTPN11GeneProductENSBTAG00000002048 (Ensembl)
  • SHP2
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
PTPN6GeneProductENSBTAG00000020294 (Ensembl)
  • SHP1
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5777
PTPRCGeneProductENSBTAG00000023144 (Ensembl)
  • CD45
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5788
RAC1ProteinENSBTAG00000009233 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
RAP1AProteinENSBTAG00000014710 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5906
RAPGEF1ProteinENSBTAG00000020791 (Ensembl)
  • C3G
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2889
RELProteinENSBTAG00000015386 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5966
RPS6ProteinENSBTAG00000014449 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6194
RPS6KA4ProteinENSBTAG00000039153 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8986
RPS6KA5ProteinENSBTAG00000010906 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9252
RPS6KB1ProteinENSBTAG00000016851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
RPTORProteinENSBTAG00000002883 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:57521
SOCS1ProteinENSBTAG00000004386 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8651
SOCS3ProteinENSBTAG00000008441 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
STAT1ProteinENSBTAG00000007867 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
STAT2ProteinENSBTAG00000004380 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6773
STAT3ProteinENSBTAG00000021523 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
STAT4ProteinENSBTAG00000046699 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6775
STAT5AProteinENSBTAG00000009496 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6776
TYK2ProteinENSBTAG00000011698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297
VAV1ProteinENSBTAG00000039160 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7409
ZAP70GeneProductENSBTAG00000005892 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7535

Annotated Interactions

No annotated interactions
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