Interferon type I signaling (Homo sapiens)

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CREBISREType I IFNsGASTRANSLATION INITIATIONmTORC1Interferon stimulated response elementType I IFN receptor complexNegative regulators of IFN transcriptionNegative regulators of IFN signalingPI3K complexGAF complexISGF3 complexGamma activated sequenceRPTORZap70MLST8VAV1PIAS3EIF4EBP1CBLGDPIRS2IFNAR1IFNAR2cRPS6KA5RAP1ASTAT3STAT2PRMT1CRKLEIF4A1CREB1CRKRac1STAT2PTPN6PIK3CDGAB2STAT1FYNPDCD4PIK3R1GNB2L1MAPK14PTPRCSTAT4EIF4EMTORRPS6KB1STAT4STAT5RPS6PTPN11MAP3K1MAP2K3EIF4BIFNAR2bRPS6KA4IRF9PIAS1TYK2MAPKAP1RELMAP2K6IRS1SOCS1FRAP1CrkLSTAT1SOCS3RAPGEF1GTPIFNAR2aJAK1LckSTAT15248P2122P18P20P28P410, 15, 2516, 31PPP12, 19PPP11, 27, 32PP17PPPPPP6PP2714PSTAT3Rac1PIK3R2PNFkBSTAT1STAT3STAT3STAT1STAT2Trans-signaling


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.


Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms

 

Bibliography

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  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. Darnell JE Jr; ''STATs and gene regulation.''; Science, 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. Novick D, Cohen B, Rubinstein M; ''Soluble interferon-alpha receptor molecules are present in body fluids.''; FEBS Lett, 1992 PubMed Europe PMC Scholia
  16. 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
  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. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  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. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. Novick D, Cohen B, Rubinstein M; ''The human interferon alpha/beta receptor: characterization and molecular cloning.''; Cell, 1994 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134387view19:16, 21 July 2024EweitzRemove template comments
129751view01:58, 22 May 2024EweitzModified title
129287view18:40, 20 March 2024Khanspersreplace graphical ptms with states, improved layout
128273view00:34, 30 January 2024EweitzStandardize case
126248view05:51, 18 April 2023EgonwLicense is CCZero
107188view14:27, 17 September 2019MaintBotChEBI identifier normalization
106622view20:49, 12 September 2019KhanspersModified description
105510view06:01, 8 August 2019KhanspersModified description
103737view20:22, 2 April 2019AlexanderPicoFixed one more complex
103736view20:21, 2 April 2019AlexanderPicoFixed groups and complexes; Fixed interaction types
94686view22:41, 4 October 2017Khanspersremoved old empty comment
85198view07:54, 25 April 2016EgonwReplaced a mim-conversion with Arrow.
85043view09:23, 10 April 2016EgonwReplaced a mim-conversion with mim-stimulation.
80201view18:55, 22 May 2015Khanspersremoved miRNA targeting for PDCD4
80161view21:11, 14 May 2015KhanspersAdded mir499a targeting of PDCD4
80148view18:08, 14 May 2015KhanspersAdded mir21 interaction with PDCD4 and lit ref
79096view15:26, 2 March 2015Sham.ukcolour
79095view15:06, 2 March 2015Sham.ukadded trans-signaling via soluble IFN receptors
78499view10:28, 7 January 2015MaintBotadded missing graphIds
73488view23:00, 29 January 2014KhanspersModified title
70094view18:35, 12 July 2013MaintBotupdating to 2013 schema
58437view10:47, 13 February 2013Sham.ukSpecify description
58436view10:45, 13 February 2013Sham.ukSpecify description
58435view10:42, 13 February 2013Sham.ukPeriodical save, work in progress
58434view10:40, 13 February 2013Sham.ukSpecify description
47017view18:44, 11 March 2012Sham.ukModified description
46968view11:45, 8 March 2012Sham.ukSpecify description
46967view11:40, 8 March 2012Sham.ukPeriodical save, work in progress
46966view11:29, 8 March 2012Sham.ukSpecify description
46965view11:23, 8 March 2012Sham.ukmodification and annotation
46964view11:20, 8 March 2012Sham.ukPeriodical save, work in progress
46963view11:09, 8 March 2012Sham.ukPeriodical save, work in progress
46962view10:59, 8 March 2012Sham.ukPeriodical save, work in progress
46961view10:49, 8 March 2012Sham.ukPeriodical save, work in progress
46960view10:38, 8 March 2012Sham.ukPeriodical save, work in progress
46959view10:28, 8 March 2012Sham.ukPeriodical save, work in progress
46958view10:17, 8 March 2012Sham.ukPeriodical save, work in progress
46909view02:38, 6 March 2012Sham.ukPeriodical save, work in progress
46908view02:34, 6 March 2012Sham.ukREDESIGN
46907view02:27, 6 March 2012Sham.ukPeriodical save, work in progress
46906view02:17, 6 March 2012Sham.ukPeriodical save, work in progress
46905view02:07, 6 March 2012Sham.ukPeriodical save, work in progress
46904view01:57, 6 March 2012Sham.ukPeriodical save, work in progress
46903view01:47, 6 March 2012Sham.ukPeriodical save, work in progress
46902view01:37, 6 March 2012Sham.ukPeriodical save, work in progress
46901view01:26, 6 March 2012Sham.ukPeriodical save, work in progress
46900view01:16, 6 March 2012Sham.ukPeriodical save, work in progress
46899view00:52, 6 March 2012Sham.ukannotaion
46898view00:45, 6 March 2012Sham.uklayout
46897view00:35, 6 March 2012Sham.ukPeriodical save, work in progress

External references

DataNodes

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NameTypeDatabase referenceComment
CBLProtein867 (Entrez Gene)
CREB1Protein1385 (Entrez Gene)
CRKGeneProduct1398 (Entrez Gene)
CRKLProtein1399 (Entrez Gene)
CrkLProtein1399 (Entrez Gene)
EIF4A1Protein1973 (Entrez Gene)
EIF4BProtein1975 (Entrez Gene)
EIF4EProtein1977 (Entrez Gene)
EIF4EBP1Protein1978 (Entrez Gene)
FRAP1Protein2475 (Entrez Gene) AKT
FYNGeneProduct2534 (Entrez Gene)
GAB2Protein9846 (Entrez Gene)
GDPMetaboliteCHEBI:17552 (ChEBI)
GNB2L1Protein10399 (Entrez Gene) RACK1
GTPMetaboliteCHEBI:15996 (ChEBI)
IFNAR1Protein3454 (Entrez Gene) INTERFERON RECEPTOR
IFNAR2aProtein3455 (Entrez Gene)
IFNAR2bProtein3455 (Entrez Gene)
IFNAR2cProtein3455 (Entrez Gene) INTERFERON RECEPTOR
IRF9Protein10379 (Entrez Gene)
IRS1Protein3667 (Entrez Gene)
IRS2Protein8660 (Entrez Gene)
JAK1GeneProduct3716 (Entrez Gene)
LckGeneProduct3932 (Entrez Gene)
MAP2K3Protein5606 (Entrez Gene)
MAP2K6Protein5608 (Entrez Gene)
MAP3K1Protein4214 (Entrez Gene)
MAPK14Protein1432 (Entrez Gene)
MAPKAP1Protein79109 (Entrez Gene)
MLST8Protein64223 (Entrez Gene)
MTORProtein2475 (Entrez Gene)
PDCD4Protein27250 (Entrez Gene)
PIAS1GeneProduct8554 (Entrez Gene)
PIAS3GeneProduct10401 (Entrez Gene)
PIK3CDProtein5293 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
PRMT1Protein3276 (Entrez Gene)
PTPN11GeneProduct5781 (Entrez Gene) SHP2
PTPN6GeneProduct5777 (Entrez Gene) SHP1
PTPRCGeneProduct5788 (Entrez Gene) CD45
RAP1AProtein5906 (Entrez Gene)
RAPGEF1Protein2889 (Entrez Gene) C3G
RELProtein5966 (Entrez Gene)
RPS6Protein6194 (Entrez Gene)
RPS6KA4Protein8986 (Entrez Gene)
RPS6KA5Protein9252 (Entrez Gene)
RPS6KB1Protein6198 (Entrez Gene)
RPTORProtein57521 (Entrez Gene)
Rac1Protein5879 (Entrez Gene)
SOCS1Protein8651 (Entrez Gene)
SOCS3Protein9021 (Entrez Gene)
STAT1Protein6772 (Entrez Gene)
STAT2Protein6773 (Entrez Gene)
STAT3Protein6774 (Entrez Gene)
STAT4Protein6775 (Entrez Gene)
STAT5Protein6776 (Entrez Gene)
TYK2Protein7297 (Entrez Gene)
VAV1Protein7409 (Entrez Gene)
Zap70GeneProduct7535 (Entrez Gene)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP585"
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