Historical Background
Interleukin (IL)-13 is an immune regulatory cytokine that plays an important role in allergy and atopic diseases (Hershey 2003; Karp 2004). It has two receptors, IL-13 receptor (IL-13R)α1 and IL-13Rα2. IL-13Rα1 monomer binds IL-13 with low affinity and mediates IL-13 cellular functions by pairing with IL-4 receptor (IL-4R)α. The IL-13 binding to IL-13Rα1/IL-4Rα heterodimer leads to activation of signal transducer and activator transcription (STAT)6 by Janus kinases (JAKs) (Miloux et al. 1997). IL-13Rα2 binds to IL-13 with high affinity but doesn’t mediate IL-13 cellular functions due to having a short cytoplasmic tail and no signaling motifs in it (Donaldson et al. 1998). The cDNA for IL-13Rα2 has first been isolated from human renal carcinoma cell lines. In 1996, Caput et al....
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References
Andrews AL, Nordgren IK, Campbell-Harding G, Holloway JW, Holgate ST, Davies DE, Tavassoli A. The association of the cytoplasmic domains of interleukin 4 receptor alpha and interleukin 13 receptor alpha 2 regulates interleukin 4 signaling. Mol BioSyst. 2013;9:3009–14.
Arima K, Sato K, Tanaka G, Kanaji S, Terada T, Honjo E, Kuroki R, Matsuo Y, Izuhara K. Characterization of the interaction between interleukin-13 and interleukin-13 receptors. J Biol Chem. 2005;280:24915–22.
Badalyan V, Thompson R, Addo K, Borthwick LA, Fisher AJ, Ort T, Myers TG, Wynn TA, Ramalingam TR. TNF-alpha/IL-17 synergy inhibits IL-13 bioactivity via IL-13Ralpha2 induction. J Allergy Clin Immunol. 2014;134:975–8 .e975
Bartolomé RA, García-Palmero I, Torres S, López-Lucendo M, Balyasnikova IV, Casal JI. IL13 receptor α2 signaling requires a scaffold protein, FAM120A, to activate the FAK and PI3K pathways in colon cancer metastasis. Cancer Res. 2015;75:2434–44.
Caput D, Laurent P, Kaghad M, Lelias J-M, Lefort S, Vita N, Ferrara P. Cloning and characterization of a specific interleukin (IL)-13 binding protein structurally related to the IL-5 receptor α chain. J Biol Chem. 1996;271:16921–6.
Chen W, Sivaprasad U, Tabata Y, Gibson AM, Stier MT, Finkelman FD, Hershey GKK. IL-13Rα2 membrane and soluble isoforms differ in humans and mice. J Immunol. 2009;183:7870–6.
Chiaramonte MG, Donaldson DD, Cheever AW, Wynn TA. An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J Clin Investig. 1999;104:777–85.
Cho WK, Lee CM, Kang MJ, Huang Y, Giordano FJ, Lee PJ, Trow TK, Homer RJ, Sessa WC, Elias JA, Lee CG. IL-13 receptor alpha2-arginase 2 pathway mediates IL-13-induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2013;304:L112–24.
Daines MO, Hershey GKK. A novel mechanism by which interferon-γ can regulate interleukin (IL)-13 responses: evidence for intracellular stores of IL-13 receptor α-2 and their rapid mobilization by interferon-γ. J Biol Chem. 2002;277:10387–93.
Donaldson DD, Whitters MJ, Fitz LJ, Neben TY, Finnerty H, Henderson SL, O’Hara RM, Beier DR, Turner KJ, Wood CR, Collins M. The murine IL-13 receptor α2: molecular cloning, characterization, and comparison with murine IL-13 receptor α1. J Immunol. 1998;161:2317–24.
Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A. IL-13 signaling through the IL-13[alpha]2 receptor is involved in induction of TGF-[beta]1 production and fibrosis. Nat Med. 2006a;12:99–106.
Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A. IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat Med. 2006b;12:99–106.
Fichtner–Feigl S, Young CA, Kitani A, Geissler EK, Schlitt HJ, Strober W. IL-13 signaling via IL-13Rα2 induces major downstream fibrogenic factors mediating fibrosis in chronic TNBS colitis. Gastroenterology. 2008;135: 2003–13.e2007.
Fujisawa T, Joshi B, Nakajima A, Puri RK. A novel role of interleukin-13 receptor alpha2 in pancreatic cancer invasion and metastasis. Cancer Res. 2009;69:8678–85.
Fujisawa T, Joshi BH, Puri RK. IL-13 regulates cancer invasion and metastasis through IL-13Rα2 via ERK/AP-1 pathway in mouse model of human ovarian cancer. Int J Cancer. 2012;131:344–56.
Gonzalez-Moreno O, Calvo A, Joshi BH, Abasolo I, Leland P, Wang Z, Montuenga L, Puri RK, Green JE. Gene expression profiling identifies IL-13 receptor alpha 2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin. Int J Cancer. 2005;114:870–8.
Granel B, Allanore Y, Chevillard C, Arnaud V, Marquet S, Weiller P-J, Durand J-M, Harlé J-R, Grange C, Frances Y, Berbis P, Gaudart J, de Micco P, Kahan A, Dessein A. IL13RA2 gene polymorphisms are associated with systemic sclerosis. J Rheumatol. 2006;33:2015–9.
Guo J, Apiou F, Mellerin M-P, Lebeau B, Jacques Y, Minvielle S. Chromosome mapping and expression of the human interleukin-13 receptor. Genomics. 1997;42:141–5.
He CH, Lee CG, Dela Cruz CS, Lee C-M, Zhou Y, Ahangari F, Ma B, Herzog EL, Rosenberg SA, Li Y, Nour AM, Parikh CR, Schmidt I, Modis Y, Cantley L, Elias JA. Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2. Cell Rep. 2013;4:830–41.
Hershey GKK. IL-13 receptors and signaling pathways: an evolving web. J Allergy Clin Immunol. 2003;111:677–90.
Jarboe JS, Johnson KR, Choi Y, Lonser RR, Park JK. Expression of interleukin-13 receptor α2 in glioblastoma multiforme: implications for targeted therapies. Cancer Res. 2007;67:7983–6.
Karp MW. Interleukin-13 in asthma pathogenesis. Curr Allergy Asthma Rep. 2004;4:123–31.
Kasaian MT, Raible D, Marquette K, Cook TA, Zhou S, Tan X-Y, Tchistiakova L. IL-13 antibodies influence IL-13 clearance in humans by modulating scavenger activity of IL-13Rα2. J Immunol. 2011;187:561–9.
Kawakami K, Takeshita F, Puri RK. Identification of distinct roles for a dileucine and a tyrosine internalization motif in the interleukin (IL)-13 binding component IL-13 receptor alpha 2 chain. J Biol Chem. 2001a;276:25114–20.
Kawakami K, Takeshita F, Puri RK. Identification of distinct roles for a dileucine and a tyrosine internalization motif in the interleukin (IL)-13 binding component IL-13 receptor α2 chain. J Biol Chem. 2001b;276:25114–20.
Kawakami M, Kawakami K, Kasperbauer JL, Hinkley LL, Tsukuda M, Strome SE, Puri RK. Interleukin-13 receptor α2 chain in human head and neck cancer serves as a unique diagnostic marker. Clin Cancer Res. 2003;9:6381–8.
Kawakami K, Terabe M, Kawakami M, Berzofsky JA, Puri RK. Characterization of a novel human tumor antigen interleukin-13 receptor α2 chain. Cancer Res. 2006;66:4434–42.
Kioi M, Kawakami K, Puri RK. Analysis of antitumor activity of an interleukin-13 (IL-13) receptor-targeted cytotoxin composed of IL-13 antagonist and pseudomonas exotoxin. Clin Cancer Res. 2004;10:6231–8.
Kioi M, Kawakami M, Shimamura T, Husain SR, Puri RK. Interleukin-13 receptor alpha2 chain: a potential biomarker and molecular target for ovarian cancer therapy. Cancer. 2006a;107:1407–18.
Kioi M, Kawakami M, Shimamura T, Husain SR, Puri RK. Interleukin-13 receptor α2 chain. Cancer. 2006b;107:1407–18.
Kioi M, Seetharam S, Puri RK. N-linked glycosylation of IL-13Rα2 is essential for optimal IL-13 inhibitory activity. FASEB J. 2006c;20:2378–80.
Lee C-M, He CH, Nour AM, Zhou Y, Ma B, Park JW, Kim KH, Cruz CD, Sharma L, Nasr ML, Modis Y, Lee CG, Elias JA. IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses. Nat Commun. 2016;7:12752.
Lupardus PJ, Birnbaum ME, Garcia KC. Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13Rα2. Structure (London, England: 1993). 2010;18:332–42.
Mentink-Kane MM, Cheever AW, Thompson RW, Hari DM, Kabatereine NB, Vennervald BJ, Ouma JH, Mwatha JK, Jones FM, Donaldson DD, Grusby MJ, Dunne DW, Wynn TA. IL-13 receptor α 2 down-modulates granulomatous inflammation and prolongs host survival in schistosomiasis. Proc Natl Acad Sci U S A. 2004;101:586–90.
Miloux B, Laurent P, Bonnin O, Lupker J, Caput D, Vita N, Ferrara P. Cloning of the human IL-13Rα1 chain and reconstitution with the IL-4Rα of a functional IL-4/IL-13 receptor complex. FEBS Lett. 1997;401:163–6.
Miyoshi M, Horiuchi H, Fukushima Y, Matsuda H, Furusawa S. Cloning of the chicken interleukin-13 receptor α2 gene and production of a specific monoclonal antibody. Dev Comp Immunol. 2007;31:394–406.
Orchansky PL, Kwan R, Lee F, Schrader JW. Characterization of the cytoplasmic domain of interleukin-13 receptor-α. J Biol Chem. 1999;274:20818–25.
Papageorgis P, Ozturk S, Lambert AW, Neophytou CM, Tzatsos A, Wong CK, Thiagalingam S, Constantinou AI. Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis. Breast Cancer Res. 2015;17:98.
Plante S, Semlali A, Joubert P, Bissonnette É, Laviolette M, Hamid Q, Chakir J. Mast cells regulate procollagen I (α1) production by bronchial fibroblasts derived from subjects with asthma through IL-4/IL-4δ2 ratio. J Allergy Clin Immunol. 2006;117:1321–7.
Puri R, Leland P, Obiri N, Husain S, Kreitman R, Haas G, Pastan I, Debinski W. Targeting of interleukin-13 receptor on human renal cell carcinoma cells by a recombinant chimeric protein composed of interleukin-13 and a truncated form of pseudomonas exotoxin A (PE38QQR). Blood. 1996;87:4333–9.
Tabata Y, Khurana Hershey GK. IL-13 receptor isoforms: breaking through the complexity. Curr Allergy Asthma Rep. 2007;7:338–45.
Warren S, Atsushi K, Stefan F-F, Ivan JF. The signaling function of the IL-13Rα2 receptor in the development of gastrointestinal fibrosis and cancer surveillance. Curr Mol Med. 2009;9:740–50.
Wood N, Whitters MJ, Jacobson BA, Witek J, Sypek JP, Kasaian M, Eppihimer MJ, Unger M, Tanaka T, Goldman SJ, Collins M, Donaldson DD, Grusby MJ. Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor α2. J Exp Med. 2003;197:703–9.
Wykosky J, Gibo DM, Stanton C, Debinski W. Interleukin-13 receptor α2, EphA2, and fos-related antigen 1 as molecular denominators of high-grade astrocytomas and specific targets for combinatorial therapy. Clin Cancer Res. 2008;14:199–208.
Zhang J-G, Hilton DJ, Willson TA, McFarlane C, Roberts BA, Moritz RL, Simpson RJ, Alexander WS, Metcalf D, Nicola NA. Identification, purification, and characterization of a soluble interleukin (IL)-13-binding protein: evidence that it is distinct from the cloned IL-13 receptor and IL-4 receptor α-chains. J Biol Chem. 1997;272:9474–80.
Zhao Z, Wang L, Xu W. IL-13Ralpha2 mediates PNR-induced migration and metastasis in ERalpha-negative breast cancer. Oncogene. 2014;34:1596.
Zhao Z, Wang L, Xu W. IL-13Rα2 mediates PNR-induced migration and metastasis in ERα-negative breast cancer. Oncogene. 2015;34:1596–607.
Zheng T, Zhu Z, Liu W, Lee CG, Chen Q, Homer RJ, Elias JA. Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro. J Allergy Clin Immunol. 2003;111:720–8.
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Jannoo, R., Kanamarlapudi, V. (2018). Interleukin-13 Receptor Subunit Alpha-2 (IL-13Rα2). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101987
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101987
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