Abstract
Murine interleukin-5 (IL-5) binds to its receptor with high and low affinity. It has been shown that the high affinity IL-5 receptor (IL-5-R) is composed of at least two membrane protein subunits and is responsible for IL-5-mediated signal transduction. One subunit of the high affinity IL-5-R is a 60 kDa membrane protein (p60 IL-5-R) whose cDNA was isolated using the anti-IL-5-R monoclonal antibody (mAb), H7. This subunit alone binds IL-5 with low affinity. The second subunit does not bind IL-5 by itself, and is expressed not only on IL-5-dependent cell lines but also on an IL-3-dependent cell line, FDC-P1. Expression of the p60 IL-5-R cDNA in FDC-P1 cells, which do not bind IL-5, reconstituted the high affinity IL-5-R. We have characterized the second subunit of the IL-5-R by using another anti-IL-5-R mAb, R52.120, and the anti-IL-3-R mAb, anti-Aic-2. The anti-Aic-2 mAb down-regulated binding of IL-5 to an IL-5-dependent cell line, Y16. Both R52.120 and anti-Aic-2 mAbs recognized membrane proteins of 130-140 kDa expressed on FDC-P1 and Y16 cells. The R52.120 mAb recognized both murine IL-3-R (AIC2A) and its homologue (AIC2B) expressed on L cells transfected with suitable cDNAs. The high affinity IL-5-R was reconstituted on an L cell transfectant co-expressing AIC2B and p60 IL-5-R, whereas only the low affinity IL-5-R was detected on a transfectant co-expressing AIC2A and p60 IL-5-R.(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bazan J. F. A novel family of growth factor receptors: a common binding domain in the growth hormone, prolactin, erythropoietin and IL-6 receptors, and the p75 IL-2 receptor beta-chain. Biochem Biophys Res Commun. 1989 Oct 31;164(2):788–795. doi: 10.1016/0006-291x(89)91528-3. [DOI] [PubMed] [Google Scholar]
- Dent L. A., Strath M., Mellor A. L., Sanderson C. J. Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med. 1990 Nov 1;172(5):1425–1431. doi: 10.1084/jem.172.5.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Enquist L. W., Vande Woude G. F., Wagner M., Smiley J. R., Summers W. C. Construction and characterization of a recombinant plasmid encoding the gene for the thymidine kinase of Herpes simplex type 1 virus. Gene. 1979 Nov;7(3-4):335–342. doi: 10.1016/0378-1119(79)90052-0. [DOI] [PubMed] [Google Scholar]
- Gearing D. P., King J. A., Gough N. M., Nicola N. A. Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. EMBO J. 1989 Dec 1;8(12):3667–3676. doi: 10.1002/j.1460-2075.1989.tb08541.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorman D. M., Itoh N., Kitamura T., Schreurs J., Yonehara S., Yahara I., Arai K., Miyajima A. Cloning and expression of a gene encoding an interleukin 3 receptor-like protein: identification of another member of the cytokine receptor gene family. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5459–5463. doi: 10.1073/pnas.87.14.5459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hatakeyama M., Mori H., Doi T., Taniguchi T. A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. Cell. 1989 Dec 1;59(5):837–845. doi: 10.1016/0092-8674(89)90607-7. [DOI] [PubMed] [Google Scholar]
- Hatakeyama M., Tsudo M., Minamoto S., Kono T., Doi T., Miyata T., Miyasaka M., Taniguchi T. Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. Science. 1989 May 5;244(4904):551–556. doi: 10.1126/science.2785715. [DOI] [PubMed] [Google Scholar]
- Hayashida K., Kitamura T., Gorman D. M., Arai K., Yokota T., Miyajima A. Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9655–9659. doi: 10.1073/pnas.87.24.9655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hibi M., Murakami M., Saito M., Hirano T., Taga T., Kishimoto T. Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell. 1990 Dec 21;63(6):1149–1157. doi: 10.1016/0092-8674(90)90411-7. [DOI] [PubMed] [Google Scholar]
- Hirai K., Yamaguchi M., Misaki Y., Takaishi T., Ohta K., Morita Y., Ito K., Miyamoto T. Enhancement of human basophil histamine release by interleukin 5. J Exp Med. 1990 Nov 1;172(5):1525–1528. doi: 10.1084/jem.172.5.1525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hitoshi Y., Yamaguchi N., Mita S., Sonoda E., Takaki S., Tominaga A., Takatsu K. Distribution of IL-5 receptor-positive B cells. Expression of IL-5 receptor on Ly-1(CD5)+ B cells. J Immunol. 1990 Jun 1;144(11):4218–4225. [PubMed] [Google Scholar]
- Isfort R. J., Ihle J. N. Multiple hematopoietic growth factors signal through tyrosine phosphorylation. Growth Factors. 1990;2(2-3):213–220. doi: 10.3109/08977199009071507. [DOI] [PubMed] [Google Scholar]
- Itoh N., Yonehara S., Schreurs J., Gorman D. M., Maruyama K., Ishii A., Yahara I., Arai K., Miyajima A. Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family. Science. 1990 Jan 19;247(4940):324–327. doi: 10.1126/science.2404337. [DOI] [PubMed] [Google Scholar]
- Kinashi T., Harada N., Severinson E., Tanabe T., Sideras P., Konishi M., Azuma C., Tominaga A., Bergstedt-Lindqvist S., Takahashi M. Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II. Nature. 1986 Nov 6;324(6092):70–73. doi: 10.1038/324070a0. [DOI] [PubMed] [Google Scholar]
- Kitamura T., Hayashida K., Sakamaki K., Yokota T., Arai K., Miyajima A. Reconstitution of functional receptors for human granulocyte/macrophage colony-stimulating factor (GM-CSF): evidence that the protein encoded by the AIC2B cDNA is a subunit of the murine GM-CSF receptor. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5082–5086. doi: 10.1073/pnas.88.12.5082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kitamura T., Takaku F., Miyajima A. IL-1 up-regulates the expression of cytokine receptors on a factor-dependent human hemopoietic cell line, TF-1. Int Immunol. 1991 Jun;3(6):571–577. doi: 10.1093/intimm/3.6.571. [DOI] [PubMed] [Google Scholar]
- Leonard W. J., Depper J. M., Crabtree G. R., Rudikoff S., Pumphrey J., Robb R. J., Krönke M., Svetlik P. B., Peffer N. J., Waldmann T. A. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):626–631. doi: 10.1038/311626a0. [DOI] [PubMed] [Google Scholar]
- Lopez A. F., Eglinton J. M., Gillis D., Park L. S., Clark S., Vadas M. A. Reciprocal inhibition of binding between interleukin 3 and granulocyte-macrophage colony-stimulating factor to human eosinophils. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7022–7026. doi: 10.1073/pnas.86.18.7022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopez A. F., Eglinton J. M., Lyons A. B., Tapley P. M., To L. B., Park L. S., Clark S. C., Vadas M. A. Human interleukin-3 inhibits the binding of granulocyte-macrophage colony-stimulating factor and interleukin-5 to basophils and strongly enhances their functional activity. J Cell Physiol. 1990 Oct;145(1):69–77. doi: 10.1002/jcp.1041450111. [DOI] [PubMed] [Google Scholar]
- Mita S., Harada N., Naomi S., Hitoshi Y., Sakamoto K., Akagi M., Tominaga A., Takatsu K. Receptors for T cell-replacing factor/interleukin 5. Specificity, quantitation, and its implication. J Exp Med. 1988 Sep 1;168(3):863–878. doi: 10.1084/jem.168.3.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mita S., Takaki S., Hitoshi Y., Rolink A. G., Tominaga A., Yamaguchi N., Takatsu K. Molecular characterization of the beta chain of the murine interleukin 5 receptor. Int Immunol. 1991 Jul;3(7):665–672. doi: 10.1093/intimm/3.7.665. [DOI] [PubMed] [Google Scholar]
- Mita S., Tominaga A., Hitoshi Y., Sakamoto K., Honjo T., Akagi M., Kikuchi Y., Yamaguchi N., Takatsu K. Characterization of high-affinity receptors for interleukin 5 on interleukin 5-dependent cell lines. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2311–2315. doi: 10.1073/pnas.86.7.2311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyazaki J., Takaki S., Araki K., Tashiro F., Tominaga A., Takatsu K., Yamamura K. Expression vector system based on the chicken beta-actin promoter directs efficient production of interleukin-5. Gene. 1989 Jul 15;79(2):269–277. doi: 10.1016/0378-1119(89)90209-6. [DOI] [PubMed] [Google Scholar]
- Murata Y., Yamaguchi N., Hitoshi Y., Tominaga A., Takatsu K. Interleukin 5 and interleukin 3 induce serine and tyrosine phosphorylations of several cellular proteins in an interleukin 5-dependent cell line. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1102–1108. doi: 10.1016/s0006-291x(05)80899-x. [DOI] [PubMed] [Google Scholar]
- Nikaido T., Shimizu A., Ishida N., Sabe H., Teshigawara K., Maeda M., Uchiyama T., Yodoi J., Honjo T. Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):631–635. doi: 10.1038/311631a0. [DOI] [PubMed] [Google Scholar]
- Park L. S., Friend D., Price V., Anderson D., Singer J., Prickett K. S., Urdal D. L. Heterogeneity in human interleukin-3 receptors. A subclass that binds human granulocyte/macrophage colony stimulating factor. J Biol Chem. 1989 Apr 5;264(10):5420–5427. [PubMed] [Google Scholar]
- Rolink A. G., Melchers F., Palacios R. Monoclonal antibodies reactive with the mouse interleukin 5 receptor. J Exp Med. 1989 May 1;169(5):1693–1701. doi: 10.1084/jem.169.5.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanderson C. J., Campbell H. D., Young I. G. Molecular and cellular biology of eosinophil differentiation factor (interleukin-5) and its effects on human and mouse B cells. Immunol Rev. 1988 Feb;102:29–50. doi: 10.1111/j.1600-065x.1988.tb00740.x. [DOI] [PubMed] [Google Scholar]
- Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
- Swain S. L., McKenzie D. T., Dutton R. W., Tonkonogy S. L., English M. The role of IL4 and IL5: characterization of a distinct helper T cell subset that makes IL4 and IL5 (Th2) and requires priming before induction of lymphokine secretion. Immunol Rev. 1988 Feb;102:77–105. doi: 10.1111/j.1600-065x.1988.tb00742.x. [DOI] [PubMed] [Google Scholar]
- Taga T., Hibi M., Hirata Y., Yamasaki K., Yasukawa K., Matsuda T., Hirano T., Kishimoto T. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell. 1989 Aug 11;58(3):573–581. doi: 10.1016/0092-8674(89)90438-8. [DOI] [PubMed] [Google Scholar]
- Takaki S., Tominaga A., Hitoshi Y., Mita S., Sonoda E., Yamaguchi N., Takatsu K. Molecular cloning and expression of the murine interleukin-5 receptor. EMBO J. 1990 Dec;9(13):4367–4374. doi: 10.1002/j.1460-2075.1990.tb07886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takatsu K., Tanaka K., Tominaga A., Kumahara Y., Hamaoka T. Antigen-induced T cell-replacing factor (TRF). III. Establishment of T cell hybrid clone continuously producing TRF and functional analysis of released TRF. J Immunol. 1980 Dec;125(6):2646–2653. [PubMed] [Google Scholar]
- Takatsu K., Tominaga A., Harada N., Mita S., Matsumoto M., Takahashi T., Kikuchi Y., Yamaguchi N. T cell-replacing factor (TRF)/interleukin 5 (IL-5): molecular and functional properties. Immunol Rev. 1988 Feb;102:107–135. doi: 10.1111/j.1600-065x.1988.tb00743.x. [DOI] [PubMed] [Google Scholar]
- Tominaga A., Mita S., Kikuchi Y., Hitoshi Y., Takatsu K., Nishikawa S., Ogawa M. Establishment of IL-5-dependent early B cell lines by long-term bone marrow cultures. Growth Factors. 1989;1(2):135–146. doi: 10.3109/08977198909029123. [DOI] [PubMed] [Google Scholar]
- Tominaga A., Takahashi T., Kikuchi Y., Mita S., Naomi S., Harada N., Yamaguchi N., Takatsu K. Role of carbohydrate moiety of IL-5. Effect of tunicamycin on the glycosylation of IL-5 and the biologic activity of deglycosylated IL-5. J Immunol. 1990 Feb 15;144(4):1345–1352. [PubMed] [Google Scholar]
- Tominaga A., Takaki S., Koyama N., Katoh S., Matsumoto R., Migita M., Hitoshi Y., Hosoya Y., Yamauchi S., Kanai Y. Transgenic mice expressing a B cell growth and differentiation factor gene (interleukin 5) develop eosinophilia and autoantibody production. J Exp Med. 1991 Feb 1;173(2):429–437. doi: 10.1084/jem.173.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamaguchi N., Hitoshi Y., Mita S., Hosoya Y., Murata Y., Kikuchi Y., Tominaga A., Takatsu K. Characterization of the murine interleukin 5 receptor by using a monoclonal antibody. Int Immunol. 1990;2(2):181–187. doi: 10.1093/intimm/2.2.181. [DOI] [PubMed] [Google Scholar]
- Yamasaki K., Taga T., Hirata Y., Yawata H., Kawanishi Y., Seed B., Taniguchi T., Hirano T., Kishimoto T. Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science. 1988 Aug 12;241(4867):825–828. doi: 10.1126/science.3136546. [DOI] [PubMed] [Google Scholar]
- Yokota T., Coffman R. L., Hagiwara H., Rennick D. M., Takebe Y., Yokota K., Gemmell L., Shrader B., Yang G., Meyerson P. Isolation and characterization of lymphokine cDNA clones encoding mouse and human IgA-enhancing factor and eosinophil colony-stimulating factor activities: relationship to interleukin 5. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7388–7392. doi: 10.1073/pnas.84.21.7388. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yonehara S., Ishii A., Yonehara M., Koyasu S., Miyajima A., Schreurs J., Arai K., Yahara I. Identification of a cell surface 105 kd protein (Aic-2 antigen) which binds interleukin-3. Int Immunol. 1990;2(2):143–150. doi: 10.1093/intimm/2.2.143. [DOI] [PubMed] [Google Scholar]