Interleukin-20 family signaling (Homo sapiens)

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7, 15, 189, 25, 33225, 15, 3210, 20-2256, 1113, 265, 15, 2612, 17, 31, 343, 5, 14, 15nucleoplasmcytosolIL20RA IL24 IL20RB IL22RA2 IL20RB IL20RA IL20RB IL20RA p-Y705-STAT3IL20RA IL22RA1:JAK1JAK1 IL19TYK2 JAK1 IL20IL20 JAK1 IL22:IL22RA1:JAK1:IL10RB:TYK2IL22RA1 JAK1 IL24 IFNL1IL22 IL20RBIFNL1 IL22RA1 IL10RB IL19:IL20RA:JAK1:IL20RBIL22:IL22RA1:JAK1IL22 JAK1 JAK1 TYK2 IL24:IL22RA1:JAK1:IL20RBp-Y705-STAT3 IL22IL20RB IL22RA2:IL22TYK2 IL10RB IL22 PTPN11TYK2 JAK1 JAK1 IL10RB:TYK2IL20:IL20RA:JAK1:IL20RBIL20RA IL22RA1:JAK1:IL20RBJAK1 MAPK1/MAPK3signalingIL24IL10RB IL20RA:JAK1IL10RB:TYK2IL20RA:JAK1:IL20RBIL22RA2JAK1 JAK1 IL20RB JAK1 IL22RA1 IL24:IL20RA:JAK1:IL20RBp-Y705-STAT3 dimerIFNLR1 IL22RA1 IFNLR1:JAK1IFNL1:IFNLR1:JAK1:IL10RB:TYK2IFNLR1 IL10RB IL24IL19 IL20RB IL22RA1 30231, 2, 4, 8, 16...2330


Description

The interleukin 20 (IL20) subfamily comprises IL19, IL20, IL22, IL24 and IL26. They are members of the larger IL10 family, but have been grouped together based on their usage of common receptor subunits and similarities in their target cell profiles and biological functions. Members of the IL20 subfamily facilitate the communication between leukocytes and epithelial cells, thereby enhancing innate defence mechanisms and tissue repair processes at epithelial surfaces. Much of the understanding of this group of cytokines is based on IL22, which is the most studied member (Rutz et al. 2014, Akdis M et al. 2016, Longsdon et al. 2012). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8854691
Reactome-version 
Reactome version: 62
Reactome Author 
Reactome Author: Jupe, Steve

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114997view16:53, 25 January 2021ReactomeTeamReactome version 75
113441view11:51, 2 November 2020ReactomeTeamReactome version 74
112642view16:02, 9 October 2020ReactomeTeamReactome version 73
101557view11:43, 1 November 2018ReactomeTeamreactome version 66
101093view21:25, 31 October 2018ReactomeTeamreactome version 65
100622view20:00, 31 October 2018ReactomeTeamreactome version 64
100173view16:44, 31 October 2018ReactomeTeamreactome version 63
99723view15:11, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99297view12:46, 31 October 2018ReactomeTeamreactome version 62
94490view08:53, 14 September 2017Mkutmonreactome pathway rename
87863view12:06, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
86561view09:21, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
IFNL1 ProteinQ8IU54 (Uniprot-TrEMBL)
IFNL1:IFNLR1:JAK1:IL10RB:TYK2ComplexR-HSA-448637 (Reactome)
IFNL1ProteinQ8IU54 (Uniprot-TrEMBL)
IFNLR1 ProteinQ8IU57 (Uniprot-TrEMBL)
IFNLR1:JAK1ComplexR-HSA-8987216 (Reactome)
IL10RB ProteinQ08334 (Uniprot-TrEMBL)
IL10RB:TYK2ComplexR-HSA-6784360 (Reactome)
IL19 ProteinQ9UHD0 (Uniprot-TrEMBL)
IL19:IL20RA:JAK1:IL20RBComplexR-HSA-448743 (Reactome)
IL19ProteinQ9UHD0 (Uniprot-TrEMBL)
IL20 ProteinQ9NYY1 (Uniprot-TrEMBL)
IL20:IL20RA:JAK1:IL20RBComplexR-HSA-8986991 (Reactome)
IL20ProteinQ9NYY1 (Uniprot-TrEMBL)
IL20RA ProteinQ9UHF4 (Uniprot-TrEMBL)
IL20RA:JAK1:IL20RBComplexR-HSA-448724 (Reactome)
IL20RA:JAK1ComplexR-HSA-8987071 (Reactome)
IL20RB ProteinQ6UXL0 (Uniprot-TrEMBL)
IL20RBProteinQ6UXL0 (Uniprot-TrEMBL)
IL22 ProteinQ9GZX6 (Uniprot-TrEMBL)
IL22:IL22RA1:JAK1:IL10RB:TYK2ComplexR-HSA-8854697 (Reactome)
IL22:IL22RA1:JAK1ComplexR-HSA-448411 (Reactome)
IL22ProteinQ9GZX6 (Uniprot-TrEMBL)
IL22RA1 ProteinQ8N6P7 (Uniprot-TrEMBL)
IL22RA1:JAK1:IL20RBComplexR-HSA-448727 (Reactome)
IL22RA1:JAK1ComplexR-HSA-8987233 (Reactome)
IL22RA2 ProteinQ969J5 (Uniprot-TrEMBL)
IL22RA2:IL22ComplexR-HSA-448738 (Reactome)
IL22RA2ProteinQ969J5 (Uniprot-TrEMBL)
IL24 ProteinQ13007 (Uniprot-TrEMBL)
IL24:IL20RA:JAK1:IL20RBComplexR-HSA-8987038 (Reactome)
IL24:IL22RA1:JAK1:IL20RBComplexR-HSA-448735 (Reactome)
IL24ProteinQ13007 (Uniprot-TrEMBL)
JAK1 ProteinP23458 (Uniprot-TrEMBL)
MAPK1/MAPK3 signalingPathwayR-HSA-5684996 (Reactome) The extracellular signal regulated kinases (ERKs) 1 and 2, also known as MAPK3 and MAPK1, are phosphorylated by the MAP2Ks 1 and 2 in response to a wide range of extracellular stimuli to promote differentiation, proliferation, cell motility, cell survivial, metabolism and transcription, among others (reviewed in Roskoski, 2012b; McKay and Morrison, 2007; Raman et al, 2007). In the classical pathway, MAPK1/3 activation is triggered by the GEF-mediated activation of RAS at the plasma membrane, leading to the activation of the RAF MAP3Ks (reviewed in McKay and Morrison, 2007; Matallanas et al, 2011; Wellbrock et al, 2004). However, many physiological and pathological stimuli have been found to activate MAPK1/3 independently of RAF and RAS, acting instead through MAP3Ks such as MOS, TPL2 and AMPK (Dawson et al, 2008; Wang et al, 2009; Kuriakose et al, 2014; Awane et al, 1999). Activated MAPK1/3 phosphorylate numerous targets in both the nucleus and cytoplasm (reviewed in Yoon and Seger, 2006; Roskoski 2012b).
PTPN11ProteinQ06124 (Uniprot-TrEMBL)
TYK2 ProteinP29597 (Uniprot-TrEMBL)
p-Y705-STAT3 ProteinP40763 (Uniprot-TrEMBL)
p-Y705-STAT3 dimerComplexR-HSA-1112526 (Reactome)
p-Y705-STAT3ProteinP40763 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
IFNL1:IFNLR1:JAK1:IL10RB:TYK2ArrowR-HSA-448661 (Reactome)
IFNL1R-HSA-448661 (Reactome)
IFNLR1:JAK1R-HSA-448661 (Reactome)
IL10RB:TYK2R-HSA-448661 (Reactome)
IL10RB:TYK2R-HSA-8854645 (Reactome)
IL19:IL20RA:JAK1:IL20RBArrowR-HSA-448728 (Reactome)
IL19R-HSA-448728 (Reactome)
IL20:IL20RA:JAK1:IL20RBArrowR-HSA-8987015 (Reactome)
IL20R-HSA-8987015 (Reactome)
IL20RA:JAK1:IL20RBArrowR-HSA-448744 (Reactome)
IL20RA:JAK1:IL20RBR-HSA-448728 (Reactome)
IL20RA:JAK1:IL20RBR-HSA-8986972 (Reactome)
IL20RA:JAK1:IL20RBR-HSA-8987015 (Reactome)
IL20RA:JAK1R-HSA-448744 (Reactome)
IL20RBR-HSA-448744 (Reactome)
IL22:IL22RA1:JAK1:IL10RB:TYK2ArrowR-HSA-8854645 (Reactome)
IL22:IL22RA1:JAK1ArrowR-HSA-448480 (Reactome)
IL22:IL22RA1:JAK1R-HSA-8854645 (Reactome)
IL22R-HSA-448480 (Reactome)
IL22R-HSA-448741 (Reactome)
IL22RA1:JAK1:IL20RBR-HSA-448708 (Reactome)
IL22RA1:JAK1R-HSA-448480 (Reactome)
IL22RA2:IL22ArrowR-HSA-448741 (Reactome)
IL22RA2:IL22TBarR-HSA-448480 (Reactome)
IL22RA2R-HSA-448741 (Reactome)
IL24:IL20RA:JAK1:IL20RBArrowR-HSA-8986972 (Reactome)
IL24:IL22RA1:JAK1:IL20RBArrowR-HSA-448708 (Reactome)
IL24R-HSA-448708 (Reactome)
IL24R-HSA-8986972 (Reactome)
R-HSA-448480 (Reactome) Temporal models suggest that the first event in IL22 receptor formation is binding of Interleukin-22 (IL22) to IL22RA1), which pre associates with JAK1 (Li et al. 2004, Jones et al. 2008, Xie et al. 2000, Xu et al. 2001).
The Interleukin-22 receptor consists of IL22RA1 and Interleukin-10 receptor subunit beta (IL10RB), which is also a component of the receptors for Interleukin-10 (IL10), Interleukin-22 (IL22), Interleukin-26 (IL26), Interleukin-28 (IL28), and Interferon lambda-1 (IFNL1).
R-HSA-448661 (Reactome) Interferon lambda-1 (IFNL1) binds Interleukin-10 receptor subunit beta (IL10RB), which is associated with Non-receptor tyrosine-protein kinase TYK2 (TYK2), and Interferon lambda receptor-1 (IFNLR1), which is associated with Tyrosine-protein kinase JAK1 (JAK1). Interferon lambda-2 (IFNL2, IL28A), Interleukin-28B (IL28B, Interferon lambda-3) and Interferon lambda-1 (IFNL1, Interleukin-29) are related cytokines, collectively known as the type III interferons. They are distantly related to the type I interferons (IFNs) and are members of the class II cytokine family, which includes type I, II, and III interferons and the Interleukin-10 family (IL10, Interleukin-19 (IL19), Interleukin-20 (IL20), Interleukin-22 (IL22), Interleukin-24 (IL24), and Interleukin-26 (IL26)). They are encoded by genes that form a cluster on 19q13. Expression of all three IFNLs can be induced by viral infection. They share a heterodimeric class II cytokine receptor that consists of IFNLR1 and interleukin-10 receptor beta (IL10RB) (Kotenko et al. 2003, Sheppard et al. 2003). IL10RB is also part of the receptor complexes for IL10, IL22, IL24 and IL26. IFNL1, IFNL2 and IFNL3, like type I IFNs, can signal through ISRE regulatory sites and are likely to provide antiviral activity by the induction of at least a subset of IFN-stimulated genes (Dumoutier et al. 2004, Gad et al 2004, Sheppard et al. 2003).
R-HSA-448708 (Reactome) Interleukin-24 (IL24) (and Interleukin-20 (IL20)) can activate a complex that consists of Interleukin-22 receptor subunit alpha-1 (IL22RA1), which is associated with Tyrosine-protein kinase JAK1 (JAK1) and Interleukin-20 receptor B (IL20RB) (Dumoutier et al. 2001, Parrish-Novak et al. 2002). As it is not clear whether the receptor can form in the absence of ligand, association of the ligand with the receptor trimer is represented here as an uncertain event.
R-HSA-448728 (Reactome) Interleukin-19 (IL19) binds a heterodimeric receptor complex that consists of Interleukin-20 Receptor subunit alpha (IL20RA) associated with Tyrosine-protein kinase JAK1 (JAK1) and Interleukin-20 receptor subunit beta (IL20RB).
Interleukin-20 receptor A (IL20RA) and Interleukin-20 receptor B (IL20RB) form a receptor complex for Interleukin-19 (IL19) (and Interleukin-20 (IL20) and Interleukin-24 (IL24)) (Gallagher et al. 2000, Blumberg et al. 2001, Parrish-Novak et al. 2002, Logsdon et al. 2012, Rutz et al. 2014, Pletnev et al. 2003).
This is a black box event because it is not clear whether the dimeric receptor can form in the absence of ligand.
R-HSA-448741 (Reactome) Interleukin-22 receptor subunit alpha-2 (IL22RA2), also known as Interleukin-22 binding protein (IL22BP), is a soluble receptor that binds Interleukin-22 (IL22) within the extracellular region, preventing IL22 from binding to the functional membrane-associated IL22 receptor (Xu et al. 2001, De Moura et al. 2009, Dumoutier et al. 2001, Kotenko et al. 2001). This may play a regulatory role in inflammation.
R-HSA-448744 (Reactome) Interleukin-20 receptor A (IL20RA) binds to Interleukin-20 receptor B (IL20RB) (Blumberg et al. 2001, Parrish-Novak et al. 2002, Logsdon et al. 2012, Rutz et al. 2014, Dumoutier et al. 2001).
This is a black box event because it is not clear whether the dimeric receptor can form in the absence of ligand.
R-HSA-6784765 (Reactome) Phosphorylated Signal transducer and activator of transcription 3 (STAT3) dimerizes after dissociating from the interleukin-19 (IL19) receptor complex (Akira et al. 1994) or Interleukin-22 (IL22) receptor complex (Lagos-Quintana et al. 2003, Sestito et al. 2011).

According to the classical model, phosphorylated Signal transducer and activator of transcription (STAT) monomers associate in an active dimer form, which is stabilized by the reciprocal interactions between a phosphorylated tyrosine residue of one and the SH2 domain of the other monomer (Shuai et al. 1994). These dimers then translocate to the nucleus (Akira et al. 1994). Recently an increasing number of studies have demonstrated the existence of STAT dimers in unstimulated cell states and the capability of STATs to exert biological functions independently of phosphorylation (Braunstein et al. 2003, Li et al. 2008, Santos & Costas-Pereira 2011). As phosphorylation of STATs is not unequivocally required for its subsequent translocation to the nucleus, this event is shown as an uncertain process.
R-HSA-8854645 (Reactome) Temporal models suggest that binding of Interleukin‑22 (IL22) to Interleukin‑22 receptor subunit alpha 1 (IL22RA1) creates a surface that is bound by the extracellular region of Interleukin‑10 receptor beta chain (IL10RB) (Li et al. 2004, Bleicher et al. 2008).
R-HSA-8986972 (Reactome) Interleukin-24 (IL24) binds a receptor complex containing Interleukin-20 Receptor subunit alpha (IL20RA) associated with Tyrosine-protein kinase JAK1 (JAK1) (Andoh et al. 2009, Logsdon et al. 2012) and Interleukin-20 receptor subunit beta (IL20RB) (Parrish Novak et al.1998). Furthermore IL24 can also bind Interleukin-22 receptor subunit alpha-1 (IL22RA1) and IL20RB (Wang et al. 2002) to form a ligand receptor complex.
As it is not clear whether the receptor complex can form in the absence of ligand, formation of the receptor dimer is represented here as an uncertain event.
R-HSA-8987015 (Reactome) Interleukin-20 (IL20) binds a heterodimeric receptor complex that consists of Interleukin-20 receptor subunit alpha (IL20RA), which is associated with Tyrosine-protein kinase JAK1 (JAK1) and Interleukin-20 receptor subunit beta (IL20RB) (Blumberg et al. 2001, Parrish-Novak et al. 2002, Logsdon et al. 2012, Rutz et al. 2014). Interleukin-20 receptor A (IL20RA) and Interleukin-20 receptor B (IL20RB) form a receptor complex for Interleukin-20 (IL20), Interleukin-19 (IL19) and Interleukin-24 (IL24) (Blumberg et al. 2001, Parrish-Novak et al. 2002, Logsdon et al. 2012, Rutz et al. 2014). IL20 can also bind a receptor complex that consists of Interleukin-22 receptor subunit alpha-1 (IL22RA1) and IL20RB (Kolumam et al. 2017). As it is not clear whether the dimeric receptor can form in the absence of ligand, formation of the receptor dimer is represented here as an uncertain black box event.
p-Y705-STAT3 dimerArrowR-HSA-6784765 (Reactome)
p-Y705-STAT3R-HSA-6784765 (Reactome)
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