Interleukin-9 signaling (Homo sapiens)

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1, 42, 8-105, 6cytosolIL9R:JAK1IL2RG JAK3 IL2RG:JAK3IL9R IL9:IL9R:JAK1:IL2RG:JAK3IL2RG IL9IL9 JAK3JAK1 JAK1 IL9R JAK3 IL2RG73


Description

Interleukin 9 (IL9) binds interleukin 9 (IL9R) and (IL2RG) to release IL9 signaling downstream cascade.

IL9R forms supramolecular clusters with Interleukin-2 receptors and MHC molecules in lipid rafts of human T lymphoma cells IL2RG is essential for IL9 dependent growth signal transduction (Kimura et al. 1995). IL9R (glycoprotein of 64 kDa) has saturable and specific binding sites with a Kd of 100 pM (Renauld et al. 1992).

The activated IL9R complex employs the Tyrosine-protein kinase (JAK1) and Tyrosine-protein JAK3 (JAK3) for subsequent activation of the Signal transducer and activator transcription (STAT) factors STAT1, STAT3 and STAT5. The activated STATs form STAT5 dimers and STAT1:STAT3 heterodimers (Neurath & Finotto 2016, Li & Rostami 2010).

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Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8985947
Reactome-version 
Reactome version: 64
Reactome Author 
Reactome Author: Jupe, Steve

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Bibliography

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  1. Nelson BH, Lord JD, Greenberg PD.; ''Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation.''; PubMed Europe PMC Scholia
  2. Chi F, Chen L, Wang C, Li L, Sun X, Xu Y, Ma T, Liu K, Ma X, Shu X.; ''JAK3 inhibitors based on thieno[3,2-d]pyrimidine scaffold: design, synthesis and bioactivity evaluation for the treatment of B-cell lymphoma.''; PubMed Europe PMC Scholia
  3. Clark JD, Flanagan ME, Telliez JB.; ''Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases.''; PubMed Europe PMC Scholia
  4. Johnston JA, Kawamura M, Kirken RA, Chen YQ, Blake TB, Shibuya K, Ortaldo JR, McVicar DW, O'Shea JJ.; ''Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2.''; PubMed Europe PMC Scholia
  5. Zhu MH, Berry JA, Russell SM, Leonard WJ.; ''Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta.''; PubMed Europe PMC Scholia
  6. Demoulin JB, Uyttenhove C, Lejeune D, Mui A, Groner B, Renauld JC.; ''STAT5 activation is required for interleukin-9-dependent growth and transformation of lymphoid cells.''; PubMed Europe PMC Scholia
  7. Wu L, Zepp JA, Qian W, Martin BN, Ouyang W, Yin W, Bunting KD, Aronica M, Erzurum S, Li X.; ''A novel IL-25 signaling pathway through STAT5.''; PubMed Europe PMC Scholia
  8. Nizsalóczki E, Csomós I, Nagy P, Fazekas Z, Goldman CK, Waldmann TA, Damjanovich S, Vámosi G, Mátyus L, Bodnár A.; ''Distinct spatial relationship of the interleukin-9 receptor with interleukin-2 receptor and major histocompatibility complex glycoproteins in human T lymphoma cells.''; PubMed Europe PMC Scholia
  9. Hofmann SR, Lam AQ, Frank S, Zhou YJ, Ramos HL, Kanno Y, Agnello D, Youle RJ, O'Shea JJ.; ''Jak3-independent trafficking of the common gamma chain receptor subunit: chaperone function of Jaks revisited.''; PubMed Europe PMC Scholia
  10. Longphre M, Li D, Gallup M, Drori E, Ordoñez CL, Redman T, Wenzel S, Bice DE, Fahy JV, Basbaum C.; ''Allergen-induced IL-9 directly stimulates mucin transcription in respiratory epithelial cells.''; PubMed Europe PMC Scholia
  11. Flanagan ME, Blumenkopf TA, Brissette WH, Brown MF, Casavant JM, Shang-Poa C, Doty JL, Elliott EA, Fisher MB, Hines M, Kent C, Kudlacz EM, Lillie BM, Magnuson KS, McCurdy SP, Munchhof MJ, Perry BD, Sawyer PS, Strelevitz TJ, Subramanyam C, Sun J, Whipple DA, Changelian PS.; ''Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection.''; PubMed Europe PMC Scholia
  12. Neurath MF, Finotto S.; ''IL-9 signaling as key driver of chronic inflammation in mucosal immunity.''; PubMed Europe PMC Scholia
  13. Cheng H, Ross JA, Frost JA, Kirken RA.; ''Phosphorylation of human Jak3 at tyrosines 904 and 939 positively regulates its activity.''; PubMed Europe PMC Scholia
  14. Haan C, Rolvering C, Raulf F, Kapp M, Drückes P, Thoma G, Behrmann I, Zerwes HG.; ''Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptors.''; PubMed Europe PMC Scholia
  15. Dhillon S.; ''Tofacitinib: A Review in Rheumatoid Arthritis.''; PubMed Europe PMC Scholia
  16. Li H, Rostami A.; ''IL-9: basic biology, signaling pathways in CD4+ T cells and implications for autoimmunity.''; PubMed Europe PMC Scholia
  17. Bauer JH, Liu KD, You Y, Lai SY, Goldsmith MA.; ''Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis.''; PubMed Europe PMC Scholia
  18. Yamasaki A, Saleh A, Koussih L, Muro S, Halayko AJ, Gounni AS.; ''IL-9 induces CCL11 expression via STAT3 signalling in human airway smooth muscle cells.''; PubMed Europe PMC Scholia
  19. Renauld JC, Druez C, Kermouni A, Houssiau F, Uyttenhove C, Van Roost E, Van Snick J.; ''Expression cloning of the murine and human interleukin 9 receptor cDNAs.''; PubMed Europe PMC Scholia
  20. Kimura Y, Takeshita T, Kondo M, Ishii N, Nakamura M, Van Snick J, Sugamura K.; ''Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor complex.''; PubMed Europe PMC Scholia
  21. Demoulin JB, Uyttenhove C, Van Roost E, DeLestré B, Donckers D, Van Snick J, Renauld JC.; ''A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9.''; PubMed Europe PMC Scholia
  22. Demoulin JB, Van Snick J, Renauld JC.; ''Interleukin-9 (IL-9) induces cell growth arrest associated with sustained signal transducer and activator of transcription activation in lymphoma cells overexpressing the IL-9 receptor.''; PubMed Europe PMC Scholia
  23. Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, Rizzuti BJ, Sawyer PS, Perry BD, Brissette WH, McCurdy SP, Kudlacz EM, Conklyn MJ, Elliott EA, Koslov ER, Fisher MB, Strelevitz TJ, Yoon K, Whipple DA, Sun J, Munchhof MJ, Doty JL, Casavant JM, Blumenkopf TA, Hines M, Brown MF, Lillie BM, Subramanyam C, Shang-Poa C, Milici AJ, Beckius GE, Moyer JD, Su C, Woodworth TG, Gaweco AS, Beals CR, Littman BH, Fisher DA, Smith JF, Zagouras P, Magna HA, Saltarelli MJ, Johnson KS, Nelms LF, Des Etages SG, Hayes LS, Kawabata TT, Finco-Kent D, Baker DL, Larson M, Si MS, Paniagua R, Higgins J, Holm B, Reitz B, Zhou YJ, Morris RE, O'Shea JJ, Borie DC.; ''Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor.''; PubMed Europe PMC Scholia
  24. Kang LY, Yang YC.; ''Activation of junB and c-myc primary response genes by interleukin 9 in a human factor-dependent cell line.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115009view16:54, 25 January 2021ReactomeTeamReactome version 75
113453view11:53, 2 November 2020ReactomeTeamReactome version 74
112653view16:03, 9 October 2020ReactomeTeamReactome version 73
101569view11:43, 1 November 2018ReactomeTeamreactome version 66
101105view21:27, 31 October 2018ReactomeTeamreactome version 65
100634view20:01, 31 October 2018ReactomeTeamreactome version 64
100184view16:46, 31 October 2018ReactomeTeamreactome version 63
99734view15:12, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99378view13:25, 31 October 2018DeSlOntology Term : 'interleukin-9 signaling pathway' added !
99367view12:48, 31 October 2018ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
IL2RG ProteinP31785 (Uniprot-TrEMBL)
IL2RG:JAK3ComplexR-HSA-451911 (Reactome)
IL2RGProteinP31785 (Uniprot-TrEMBL)
IL9 ProteinP15248 (Uniprot-TrEMBL)
IL9:IL9R:JAK1:IL2RG:JAK3ComplexR-HSA-449785 (Reactome)
IL9ProteinP15248 (Uniprot-TrEMBL)
IL9R ProteinQ01113 (Uniprot-TrEMBL)
IL9R:JAK1ComplexR-HSA-8985962 (Reactome) JAK1 was constitutively associated with the Interleukin-9 receptor (IL9RA) (Demulin et al. 1996).
JAK1 ProteinP23458 (Uniprot-TrEMBL)
JAK3 ProteinP52333 (Uniprot-TrEMBL)
JAK3ProteinP52333 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
IL2RG:JAK3ArrowR-HSA-451895 (Reactome)
IL2RG:JAK3R-HSA-8963734 (Reactome)
IL2RGR-HSA-451895 (Reactome)
IL9:IL9R:JAK1:IL2RG:JAK3ArrowR-HSA-8963734 (Reactome)
IL9R-HSA-8963734 (Reactome)
IL9R:JAK1R-HSA-8963734 (Reactome)
JAK3R-HSA-451895 (Reactome)
R-HSA-451895 (Reactome) Cytokine receptor common subunit gamma (IL2RG, IL-2 receptor gamma chain, Gc) associates with Tyrosine-protein kinase JAK3 (JAK3). The carboxyl-terminal region of IL2RG isimportant for this association (Miyazaki et al. 1994, Zhu et al. 1998, Russel et al. 2004, Chen et al.1997, Nelson et al.1994).
R-HSA-8963734 (Reactome) Interleukin-9 (IL9) binds to the Interleukin-9 receptor (IL9R) and Cytokine receptor common subunit gamma (IL2RG) forming a ligand-receptor complex (Kimura et al 1995, Nizsalóczki et al. 2014). IL2RG is essential for IL9 dependent growth signal transduction (Kimura et al. 1995). IL9R (glycoprotein of 64 kDa) has saturable and specific binding sites with a Kd of 100 pM (Renauld et al. 1992). IL9R forms supramolecular clusters with Interleukin-2 receptors and MHC molecules in lipid rafts of human T lymphoma cells so It is suggested that interactions within these clusters could affect the assembly and signaling capability of the receptors (Nizsalóczki et al. 2014). Moreover, there is evidence that Tyrosine protein kinase JAK1 (JAK1) cooperates with Tyrosine protein kinase JAK3 (JAK3) in signaling through IL2RG containing receptors (Haan et al. 2011).
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