Interferon gamma signaling (Homo sapiens)

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1-46, 7, 10-1539, 4028-3023-2541-4432, 332016-198, 9, 44-4834-3637, 3821, 2220, 25-2728, 30, 31lysosomal lumencytosolendoplasmic reticulum lumennucleoplasmSP100ATPATPBeta-2-microglobulinSTAT1 bound to p-IFNGR1FCGRSUMO1OrthophosphateIFNG:p-IFNGR1:p-JAK1:IFNGR2:p-JAK2ADPGAS promoter region in IFNG-regulated genesGAF bound to GAS promoter elementIFNG-activated factor (GAF)PAF receptorIFNG:IFNGR1:JAK1:IFNGR2:JAK2PTPs-SHP1/2/PTP1BATPGamma-interferon-inducible lysosomal thiol reductaseHLA IIClass I MHC heavy chain (MHC HC)STAT1-alphaIFNGR1:JAK1:INFG2:JAK2IFNG-activated factor (GAF)MHC class II transactivatorATPSOCS-1 and SOCS-3IFN-gamma upregulated CAMsPMLIFNG:IFNGR1:JAK1:IFNGR2:p-JAK2p-STAT1(Y701) bound to p-IFNGR1H2Op-STAT1 dimer:PIAS:SUMO1TC-PTPaADPIFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2ADPIFNG homodimerSTAT1OAS proteinsADPIFNG:IFNGR1:JAK1:IFNGR2:p-JAK2:SOCS-1/-3p-STAT1 dimer bound to p-IFNGR1H2OMetallothionein-2OrthophosphateADPATPIRF 1-9CaMKII and PKC-deltaPIAS1GBPPTP1BSHP18, 956, 7


Description

Interferon-gamma (IFN-gamma) belongs to the type II interferon family and is secreted by activated immune cells-primarily T and NK cells, but also B-cells and APC. INFG exerts its effect on cells by interacting with the specific IFN-gamma receptor (IFNGR). IFNGR consists of two chains, namely IFNGR1 (also known as the IFNGR alpha chain) and IFNGR2 (also known as the IFNGR beta chain). IFNGR1 is the ligand binding receptor and is required but not sufficient for signal transduction, whereas IFNGR2 do not bind IFNG independently but mainly plays a role in IFNG signaling and is generally the limiting factor in IFNG responsiveness. Both IFNGR chains lack intrinsic kinase/phosphatase activity and thus rely on other signaling proteins like Janus-activated kinase 1 (JAK1), JAK2 and Signal transducer and activator of transcription 1 (STAT-1) for signal transduction. IFNGR complex in its resting state is a preformed tetramer and upon IFNG association undergoes a conformational change. This conformational change induces the phosphorylation and activation of JAK1, JAK2, and STAT1 which in turn induces genes containing the gamma-interferon activation sequence (GAS) in the promoter.

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Bibliography

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  1. Kotenko SV, Izotova LS, Pollack BP, Mariano TM, Donnelly RJ, Muthukumaran G, Cook JR, Garotta G, Silvennoinen O, Ihle JN.; ''Interaction between the components of the interferon gamma receptor complex.''; PubMed Europe PMC Scholia
  2. ten Hoeve J, de Jesus Ibarra-Sanchez M, Fu Y, Zhu W, Tremblay M, David M, Shuai K.; ''Identification of a nuclear Stat1 protein tyrosine phosphatase.''; PubMed Europe PMC Scholia
  3. Martinez FO, Gordon S, Locati M, Mantovani A.; ''Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.''; PubMed Europe PMC Scholia
  4. Briscoe J, Rogers NC, Witthuhn BA, Watling D, Harpur AG, Wilks AF, Stark GR, Ihle JN, Kerr IM.; ''Kinase-negative mutants of JAK1 can sustain interferon-gamma-inducible gene expression but not an antiviral state.''; PubMed Europe PMC Scholia
  5. Aaronson DS, Horvath CM.; ''A road map for those who don't know JAK-STAT.''; PubMed Europe PMC Scholia
  6. Feng J, Witthuhn BA, Matsuda T, Kohlhuber F, Kerr IM, Ihle JN.; ''Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop.''; PubMed Europe PMC Scholia
  7. Mowen K, David M.; ''Regulation of STAT1 nuclear export by Jak1.''; PubMed Europe PMC Scholia
  8. Costa-Pereira AP, Hermanns HM, Is'harc H, Williams TM, Watling D, Arulampalam V, Newman SJ, Heinrich PC, Kerr IM.; ''Signaling through a mutant IFN-gamma receptor.''; PubMed Europe PMC Scholia
  9. Pestka S, Kotenko SV, Muthukumaran G, Izotova LS, Cook JR, Garotta G.; ''The interferon gamma (IFN-gamma) receptor: a paradigm for the multichain cytokine receptor.''; PubMed Europe PMC Scholia
  10. Strehlow I, Decker T.; ''Transcriptional induction of IFN-gamma-responsive genes is modulated by DNA surrounding the interferon stimulation response element.''; PubMed Europe PMC Scholia
  11. McBride KM, Reich NC.; ''The ins and outs of STAT1 nuclear transport.''; PubMed Europe PMC Scholia
  12. Krause CD, Mei E, Xie J, Jia Y, Bopp MA, Hochstrasser RM, Pestka S.; ''Seeing the light: preassembly and ligand-induced changes of the interferon gamma receptor complex in cells.''; PubMed Europe PMC Scholia
  13. Krause CD, Lavnikova N, Xie J, Mei E, Mirochnitchenko OV, Jia Y, Hochstrasser RM, Pestka S.; ''Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases, Stat1 and the receptor chains.''; PubMed Europe PMC Scholia
  14. Simoncic PD, Lee-Loy A, Barber DL, Tremblay ML, McGlade CJ.; ''The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3.''; PubMed Europe PMC Scholia
  15. Bach EA, Aguet M, Schreiber RD.; ''The IFN gamma receptor: a paradigm for cytokine receptor signaling.''; PubMed Europe PMC Scholia
  16. Ouellet S, Müller E, Rola-Pleszczynski M.; ''IFN-gamma up-regulates platelet-activating factor receptor gene expression in human monocytes.''; PubMed Europe PMC Scholia
  17. Ealick SE, Cook WJ, Vijay-Kumar S, Carson M, Nagabhushan TL, Trotta PP, Bugg CE.; ''Three-dimensional structure of recombinant human interferon-gamma.''; PubMed Europe PMC Scholia
  18. Walter MR, Windsor WT, Nagabhushan TL, Lundell DJ, Lunn CA, Zauodny PJ, Narula SK.; ''Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor.''; PubMed Europe PMC Scholia
  19. Shuai K, Horvath CM, Huang LH, Qureshi SA, Cowburn D, Darnell JE.; ''Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions.''; PubMed Europe PMC Scholia
  20. Stratowa C, Audette M.; ''Transcriptional regulation of the human intercellular adhesion molecule-1 gene: a short overview.''; PubMed Europe PMC Scholia
  21. Ungureanu D, Vanhatupa S, Kotaja N, Yang J, Aittomaki S, Jänne OA, Palvimo JJ, Silvennoinen O.; ''PIAS proteins promote SUMO-1 conjugation to STAT1.''; PubMed Europe PMC Scholia
  22. Rosenman SJ, Shrikant P, Dubb L, Benveniste EN, Ransohoff RM.; ''Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines.''; PubMed Europe PMC Scholia
  23. Matsuda T, Feng J, Witthuhn BA, Sekine Y, Ihle JN.; ''Determination of the transphosphorylation sites of Jak2 kinase.''; PubMed Europe PMC Scholia
  24. Sakatsume M, Igarashi K, Winestock KD, Garotta G, Larner AC, Finbloom DS.; ''The Jak kinases differentially associate with the alpha and beta (accessory factor) chains of the interferon gamma receptor to form a functional receptor unit capable of activating STAT transcription factors.''; PubMed Europe PMC Scholia
  25. Nair JS, DaFonseca CJ, Tjernberg A, Sun W, Darnell JE, Chait BT, Zhang JJ.; ''Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.''; PubMed Europe PMC Scholia
  26. Huang F, Xiao H, Sun BL, Yang RG.; ''Characterization of TRIM62 as a RING finger E3 ubiquitin ligase and its subcellular localization.''; PubMed Europe PMC Scholia
  27. Gough DJ, Levy DE, Johnstone RW, Clarke CJ.; ''IFNgamma signaling-does it mean JAK-STAT?''; PubMed Europe PMC Scholia
  28. Shuai K, Stark GR, Kerr IM, Darnell JE.; ''A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma.''; PubMed Europe PMC Scholia
  29. Wenta N, Strauss H, Meyer S, Vinkemeier U.; ''Tyrosine phosphorylation regulates the partitioning of STAT1 between different dimer conformations.''; PubMed Europe PMC Scholia
  30. Quintás-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, Caulder E, Wen X, Li Y, Waeltz P, Rupar M, Burn T, Lo Y, Kelley J, Covington M, Shepard S, Rodgers JD, Haley P, Kantarjian H, Fridman JS, Verstovsek S.; ''Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms.''; PubMed Europe PMC Scholia
  31. Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chène C, Fountoulakis M, Garotta G, Winkler FK, Ealick SE.; ''Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex.''; PubMed Europe PMC Scholia
  32. Fountoulakis M, Zulauf M, Lustig A, Garotta G.; ''Stoichiometry of interaction between interferon gamma and its receptor.''; PubMed Europe PMC Scholia
  33. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF, Wen X, Shi J, McGee R, Haley PJ, Shepard S, Rodgers JD, Yeleswaram S, Hollis G, Newton RC, Metcalf B, Friedman SM, Vaddi K.; ''Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050.''; PubMed Europe PMC Scholia
  34. Hanan EJ, van Abbema A, Barrett K, Blair WS, Blaney J, Chang C, Eigenbrot C, Flynn S, Gibbons P, Hurley CA, Kenny JR, Kulagowski J, Lee L, Magnuson SR, Morris C, Murray J, Pastor RM, Rawson T, Siu M, Ultsch M, Zhou A, Sampath D, Lyssikatos JP.; ''Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors.''; PubMed Europe PMC Scholia
  35. Lew DJ, Decker T, Strehlow I, Darnell JE.; ''Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons.''; PubMed Europe PMC Scholia
  36. Igarashi K, Garotta G, Ozmen L, Ziemiecki A, Wilks AF, Harpur AG, Larner AC, Finbloom DS.; ''Interferon-gamma induces tyrosine phosphorylation of interferon-gamma receptor and regulated association of protein tyrosine kinases, Jak1 and Jak2, with its receptor.''; PubMed Europe PMC Scholia
  37. Greenlund AC, Morales MO, Viviano BL, Yan H, Krolewski J, Schreiber RD.; ''Stat recruitment by tyrosine-phosphorylated cytokine receptors: an ordered reversible affinity-driven process.''; PubMed Europe PMC Scholia
  38. Rupper AC, Cardelli JA.; ''Induction of guanylate binding protein 5 by gamma interferon increases susceptibility to Salmonella enterica serovar Typhimurium-induced pyroptosis in RAW 264.7 cells.''; PubMed Europe PMC Scholia
  39. Kaplan DH, Greenlund AC, Tanner JW, Shaw AS, Schreiber RD.; ''Identification of an interferon-gamma receptor alpha chain sequence required for JAK-1 binding.''; PubMed Europe PMC Scholia
  40. Liao J, Fu Y, Shuai K.; ''Distinct roles of the NH2- and COOH-terminal domains of the protein inhibitor of activated signal transducer and activator of transcription (STAT) 1 (PIAS1) in cytokine-induced PIAS1-Stat1 interaction.''; PubMed Europe PMC Scholia
  41. Pearse RN, Feinman R, Shuai K, Darnell JE, Ravetch JV.; ''Interferon gamma-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that includes the 91-kDa subunit of transcription factor ISGF3.''; PubMed Europe PMC Scholia
  42. Decker T, Lew DJ, Mirkovitch J, Darnell JE.; ''Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor.''; PubMed Europe PMC Scholia
  43. Palvimo JJ.; ''PIAS proteins as regulators of small ubiquitin-related modifier (SUMO) modifications and transcription.''; PubMed Europe PMC Scholia
  44. Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A.; ''The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop.''; PubMed Europe PMC Scholia
  45. Boehm U, Klamp T, Groot M, Howard JC.; ''Cellular responses to interferon-gamma.''; PubMed Europe PMC Scholia
  46. Quelle FW, Thierfelder W, Witthuhn BA, Tang B, Cohen S, Ihle JN.; ''Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor.''; PubMed Europe PMC Scholia
  47. Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A.; ''Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain.''; PubMed Europe PMC Scholia
  48. Ozato K, Shin DM, Chang TH, Morse HC.; ''TRIM family proteins and their emerging roles in innate immunity.''; PubMed Europe PMC Scholia
  49. DeVries TA, Kalkofen RL, Matassa AA, Reyland ME.; ''Protein kinase Cdelta regulates apoptosis via activation of STAT1.''; PubMed Europe PMC Scholia
  50. Rajsbaum R, Stoye JP, O'Garra A.; ''Type I interferon-dependent and -independent expression of tripartite motif proteins in immune cells.''; PubMed Europe PMC Scholia
  51. Greenlund AC, Farrar MA, Viviano BL, Schreiber RD.; ''Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91).''; PubMed Europe PMC Scholia
  52. Shuai K, Schindler C, Prezioso VR, Darnell JE.; ''Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein.''; PubMed Europe PMC Scholia
  53. Schroder K, Hertzog PJ, Ravasi T, Hume DA.; ''Interferon-gamma: an overview of signals, mechanisms and functions.''; PubMed Europe PMC Scholia
  54. Argetsinger LS, Kouadio JL, Steen H, Stensballe A, Jensen ON, Carter-Su C.; ''Autophosphorylation of JAK2 on tyrosines 221 and 570 regulates its activity.''; PubMed Europe PMC Scholia
  55. Argetsinger LS, Stuckey JA, Robertson SA, Koleva RI, Cline JM, Marto JA, Myers MG, Carter-Su C.; ''Tyrosines 868, 966, and 972 in the kinase domain of JAK2 are autophosphorylated and required for maximal JAK2 kinase activity.''; PubMed Europe PMC Scholia
  56. Clark JD, Flanagan ME, Telliez JB.; ''Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115093view17:04, 25 January 2021ReactomeTeamReactome version 75
113535view12:01, 2 November 2020ReactomeTeamReactome version 74
112733view16:13, 9 October 2020ReactomeTeamReactome version 73
101649view11:51, 1 November 2018ReactomeTeamreactome version 66
101185view21:39, 31 October 2018ReactomeTeamreactome version 65
100711view20:11, 31 October 2018ReactomeTeamreactome version 64
100261view16:56, 31 October 2018ReactomeTeamreactome version 63
99814view15:20, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99357view12:48, 31 October 2018ReactomeTeamreactome version 62
93905view13:44, 16 August 2017ReactomeTeamreactome version 61
93478view11:24, 9 August 2017ReactomeTeamreactome version 61
86576view09:21, 11 July 2016ReactomeTeamreactome version 56
83234view10:27, 18 November 2015ReactomeTeamVersion54
81633view13:10, 21 August 2015ReactomeTeamVersion53
77096view08:39, 17 July 2014ReactomeTeamFixed remaining interactions
76802view12:18, 16 July 2014ReactomeTeamFixed remaining interactions
76125view10:19, 11 June 2014ReactomeTeamRe-fixing comment source
75837view11:40, 10 June 2014ReactomeTeamReactome 48 Update
75198view09:43, 9 May 2014AnweshaFixing comment source for displaying WikiPathways description
74845view10:07, 30 April 2014ReactomeTeamReactome46
44865view09:58, 6 October 2011MartijnVanIerselOntology Term : 'immune response pathway' added !
42056view21:53, 4 March 2011MaintBotAutomatic update
39862view05:53, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Beta-2-

microglobulin

ProteinP61769 (UniProt)
CaMKII and PKC-delta ProteinREACT_26704 (Reactome)
Class I MHC

heavy chain (MHC HC)

ProteinREACT_26784 (Reactome)
FCGR ProteinREACT_26475 (Reactome)
GAF bound to GAS

promoter element

ComplexREACT_25470 (Reactome)
GAS promoter region

in IFNG-regulated genes

UnknownREACT_26763 (Reactome)
GBP ProteinREACT_26189 (Reactome)
Gamma-interferon-

inducible lysosomal thiol reductase

ProteinP13284 (UniProt)
H2O Metabolite15377 (ChEBI)
HLA II ProteinREACT_13194 (Reactome)
IFN-gamma

upregulated CAMs

ProteinREACT_26072 (Reactome)
IFNG homodimer ComplexREACT_26955 (Reactome)
IFNG-activated

factor (GAF)

ComplexREACT_26144 (Reactome)
IFNG-activated

factor (GAF)

ComplexREACT_26637 (Reactome)
IFNG:IFNGR1:JAK1:

IFNGR2:JAK2

ComplexREACT_25865 (Reactome)
IFNG:IFNGR1:JAK1:

IFNGR2:p-JAK2

ComplexREACT_26738 (Reactome)
IFNG:IFNGR1:JAK1:

IFNGR2:p-JAK2: SOCS-1/-3

ComplexREACT_26775 (Reactome)
IFNG:IFNGR1:p-

JAK1:IFNGR2:p- JAK2

ComplexREACT_26286 (Reactome)
IFNG:p-IFNGR1:p-

JAK1:IFNGR2:p- JAK2

ComplexREACT_25650 (Reactome)
IFNGR1:JAK1:

INFG2:JAK2

ComplexREACT_25803 (Reactome)
IRF 1-9 ProteinREACT_26465 (Reactome)
MHC class II

transactivator

ProteinP33076 (UniProt)
Metallothionein-2 ProteinP02795 (UniProt)
OAS proteins ProteinREACT_26755 (Reactome)
Orthophosphate Metabolite18367 (ChEBI)
PAF receptor ProteinP25105 (UniProt)
PIAS1 ProteinO75925 (UniProt)
PML ProteinP29590 (UniProt)
PTP1B ProteinP18031 (UniProt)
PTPs-

SHP1/2/PTP1B

ProteinREACT_26675 (Reactome)
SHP1 ProteinP29350 (UniProt)
SOCS-1 and

SOCS-3

ProteinREACT_25587 (Reactome)
SP100 ProteinP23497 (UniProt)
STAT1 ProteinP42224-1 (UniProt)
STAT1 bound to p-

IFNGR1

ComplexREACT_26587 (Reactome)
STAT1-alpha ProteinP42224-1 (UniProt)
SUMO1 ProteinP63165 (UniProt)
TC-PTPa ProteinP17706-2 (UniProt)
p-STAT1 dimer

bound to p-IFNGR1

ComplexREACT_25936 (Reactome)
p-STAT1 dimer:

PIAS:SUMO1

ComplexREACT_25840 (Reactome)
p-STAT1(Y701)

bound to p-IFNGR1

ComplexREACT_26108 (Reactome)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1836"
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