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Molecular Cloning of the Rat IL-13 Alpha 2 Receptor CDNA and Its Expression in Rat Tissues

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Abstract

The interleukin 13 alpha 2 receptor (IL-13Rα2) is highly expressed in human glioma cells. As a consequence this receptor has been proposed as a potential target for immunotherapeutic approaches for treating brain tumors. In developing animal models that may utilize the IL-13Rα2 receptor as an immunotherapeutic target, only the murine gene sequence has thus far been elucidated. The purpose of the present study, therefore, was to determine the gene sequence and tissue distribution of IL-13Rα2 in the rat. A search of the NCBI expressed sequence tag (EST) database with human and mouse IL-13Rα2 gene sequences identified a rat EST with high homology to the human and mouse IL-13Rα2 conserved region. Based on the sequence information, a 1917 bp rat IL-13Rα2 cDNA was cloned using the 5′ and 3′ RACE PCR technique. The cloned rat IL-13Rα2 cDNA contains a full-length 1158 bp open reading frame. The deduced protein is 91.2% and 54.2% homologous to mouse and human IL-13Rα2, respectively, at the amino acid level. Analysis shows that the rat IL-13Rα2 is structurally conserved and similar to human and mouse. It has a very short cytoplasmic domain, an extracellular domain containing an N-terminal fibronectin type III domain, four putative N-glycosylation sites, and a growth factor and cytokine receptor family motif WSEWS. Using RT-PCR techniques, the mRNA of rat IL-13Rα2 was detected in rat brain, spleen, liver, thymus, stomach, testis, and three rat glioblastoma cell lines C6, A15A5 and 9L. The cloning of rat IL-13Rα2 may be helpful to establish a rat model for IL-13Rα2 related glioma therapies.

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References

  1. Punnonen J, Aversa G, Cocks BG, McKenzie AN, Menon S, Zurawski G, deWaal Malefyt R, de Vries JE: Interleukin 13 induces interleukin 4-independent igG4 and IgE synthesis and CD 23 expression by human B cells. Proc Natl Acad Sci USA 90: 3730–3734, 1993

    Google Scholar 

  2. Minty A, Chalon P, Derocq JM, Dumont X, Guillemot JC, Kaghad M, Labit C, Leplatois P, Liauzun P, Miloux B: Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature 362: 248–250, 1993

    Google Scholar 

  3. McKenzie ANJ, Culpepper JA, Malefyt RDW, Briere F, Punnonen J, Aversa G, Sato A, Dang W, Cocks BG, Menon S, Vries JED, Banchereau J, Zurawski G: Interleukin-13, a T cell derived cytokine that regulates human monocyte and B-cell function. Proc Natl Acad Sci USA 90: 3735–3739, 1993

    Google Scholar 

  4. Debinski W, Obiri NI, Pastan I, Puri RK: A novel chimeric protein composed of interleukin 13 and pseudomonas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4: J Biol Chem 270: 16775–16780, 1995

    Google Scholar 

  5. Obiri NI, Leland P, Murata T, Debinski W, Puri RK: The IL-13 receptor structure differs on various cell types and may share more than one component with IL-4 receptor. J Immunol 158: 756–764, 1997

    Google Scholar 

  6. Hilton DJ, Zhang JG, Metcalf D, Alexander WS, Nicola NA, Willson TA: Cloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor. Proc Natl Acad Sci USA 93: 497–501, 1996

    Google Scholar 

  7. Vita N, Lefort S, Laurent P, Caput D, Ferrara P: Characterization and comparison of the interleukin 13 receptor with the interleukin 4 receptor on several cell types. J Biol Chem 270: 3512–3517, 1995

    Google Scholar 

  8. Obiri NI, Debinski W, Leonard WJ, Puri RK: Receptor for interleukin 13. Interaction with interleukin 4 by a mechanism that does not involve the common gamma chain shared by receptors for interleukins 2, 4, 7, 9, and 15. J Biol Chem 270: 8797–8804, 1995

    Google Scholar 

  9. Caput D, Laurent P, Kaghad M, Lelias JM, Lefort S, Vita N, Ferrara P: Cloning and characterization of a specific interleukin (IL)-13 binding protein structurally related to the IL-5 receptor alpha chain. J Biol Chem 271: 16921–16926, 1996

    Google Scholar 

  10. Debinski W, Slagle B, Gibo DM, Powers SK, Gillespie GY: Expression of a restrictive receptor for interleukin 13 is associated with glial transformation. J Neurooncol 48: 103–111, 2000

    Google Scholar 

  11. Debinski W, Gibo DM: Molecular expression analysis of restrictive receptor for interleukin 13, a brain tumorassociated cancer/Testis antigen. Mol Med 6: 440–449, 2000

    Google Scholar 

  12. Liu H, Jacobs BS, Liu J, Prayson RA, Estes ML, Barnett GH, Barna BP: interleukin-13 sensitivity and receptor phenotypes of human glial cell lines: Non-neoplastic glia and low-grade astrocytoma differ from malignant glioma. Cancer Immunol Immunother 49: 319–324, 2000

    Google Scholar 

  13. Joshi BH, Plautz GE, Puri RK: Interleukin-13 receptor á chain: a novel tumor-associated transmembrane protein in primary explants of human malignant gliomas. Cancer Res 60: 1168–1172, 2000

    Google Scholar 

  14. Husain SR, Joshi BH, Puri RK: Interleukin-13 receptor as a unique target for anti-glioblastoma therapy. Int J Cancer 92: 168–175, 2001

    Google Scholar 

  15. Debinski W, Gibo DM, Obiri NI, Kealiher A, Puri RK: Novel anti-brain tumor cytotoxins specific for cancer cells. Nat Biotechnol 16: 449–453, 1998

    Google Scholar 

  16. Nash KT, Thompson JP, Debinski W: Molecular targeting of malignant gliomas with novel multiply-mutated interleukin 13-based cytotoxins. Crit Rev Oncol Hematol 39: 87–98, 2001

    Google Scholar 

  17. Kawakami K, Kawakami M, Joshi BH, Puri RK: Interleukin-13 receptor-targeted cancer therapy in an immunodeficient animal model of human head and neck cancer. Cancer Res 61: 6194–6200, 2001

    Google Scholar 

  18. Kawakami K, Joshi BH, Puri RK: Sensitization of cancer cells to interleukin 13-pseudomonas exotoxin-induced cell death by gene transfer of interleukin 13 receptor alpha chain. Hum Gene Ther 11: 1829–1835, 2000

    Google Scholar 

  19. Donaldson DD, Whitters MJ, Fitz LJ, Neben TY, Finnerty H, Henderson SL, O'Hara RM Jr, Beier DR, Turner KJ, Wood CR, Collins M: The murine IL-13 receptor alpha 2: molecular cloning, characterization, and comparison with murine IL-13 receptor alpha 1. J Immunol 161: 2317–2324, 1998

    Google Scholar 

  20. Zhang JG, 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 alpha-chains. J Biol Chem 272: 9474–9480, 1997

    Google Scholar 

  21. Murata T, Obiri NI, Debinski W, Puri RK: Structure of IL-13 receptor: analysis of subunit composition in cancer and immune cells. Biochem Biophys Res Commun 238: 90–94, 1997

    Google Scholar 

  22. Bernard J, Treton D, Vermot-Desroches C, Boden C, Horellou P, Angevin E, Galanaud P, Wijdenes J, Richard Y: Expression of interleukin 13 receptor in glioma and renal cell carcinoma: IL13Ralpha2 as a decoy receptor for IL13. Lab Invest 81: 1223–1231, 2001

    Google Scholar 

  23. Kawakami K, Taguchi J, Murata T, Puri RK: The interleukin-13 receptor alpha2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway. Blood 97: 2673–2679, 2001

    Google Scholar 

  24. Guo J, Apiou F, Mellerin MP, Lebeau B, Jacques Y, Minvielle S: Chromosome mapping and expression of the human interleukin-13 receptor. Genomics 42: 141–145, 1997

    Google Scholar 

  25. Sadanaga N, Nagashima H, Mashino K, Tahara K, Yamaguchi H, Ohta M, Fujie T, Tanaka F, Inoue H, Takesako K, Akiyoshi T, Mori M: Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas. Clin Cancer Res 7(8): 2277–2284, 2001

    Google Scholar 

  26. Dutoit V, Rubio-Godoy V, Dietrich PY, Quiqueres AL, Schnuriger V, Rimoldi D, Lienard D, Speiser D, Guillaume P, Batard P, Cerottini JC, Romero P, Valmori D: Heterogeneous T-cell response to MAGE-A10(254–262): high avidity-specific cytolytic T lymphocytes show superior antitumor activity. Cancer Res 61: 5850–5856, 2001

    Google Scholar 

  27. Kanaoka S, Yamasaki S, Okino T, Inoue N, Shimada Y, Kaneko M, Otaka A, Fujii N, Imamura M: Induction of human leukocyte antigen (HLA)-A2-restricted and MAGE-3-gene-derived peptide-specific cytolytic T lymphocytes using cultured dendritic cells from an HLA-A2 esophageal cancer patient. J Surg Oncol 71: 16–21, 1999

    Google Scholar 

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Wu, Ah., Low, W.C. Molecular Cloning of the Rat IL-13 Alpha 2 Receptor CDNA and Its Expression in Rat Tissues. J Neurooncol 59, 99–105 (2002). https://doi.org/10.1023/A:1019690120307

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