International Immunology, Vol. 12, No. 11, 1499-1509,
November 2000
© 2000 Japanese Society for Immunology
Characterization of IL-4 and IL-13 signals dependent on the human IL-13 receptor 
chain 1: redundancy of requirement of tyrosine residue for STAT3 activation
1 Department of Clinical Chemistry and Laboratory Medicine, and
2 Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
3 R & D Institute, UNITIKA, Ltd, 23 Ujikozakura, Uji, 611-0021 Japan
4 Department of Immunology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Osaka, Japan
Correspondence to: K. Izuhara (Present address: Department of Biochemistry, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan)
IL-4 and IL-13 are pleiotropic cytokines whose biological activities overlap with each other. IL-13 receptor 
chain 1 (IL-13R1) is necessary for binding to IL-13, and the heterodimer composed of IL-13R1 and IL-4R chain transduces IL-13 and IL-4 signals; however, the functional mapping of the intracellular domain of IL-13R1 is not fully understood. In this study, we constructed wild and mutated types of human IL-13R1, and analyzed IL-4 and IL-13 signals using an IL-13R1-transfected human B cell line. Expression of IL-13R1 evoked STAT3 activation by IL-4 and IL-13, and in stimulated human B cells, on which IL-13R1 was highly expressed, IL-4 and IL-13 induced STAT3 activation. Replacement of the two tyrosine residues completely abolished STAT3 activation, although replacing either tyrosine residue alone retained it. Furthermore, we found that the Box1 region and the C-terminal tail of IL-13R1 were critical for binding to Tyk2, and activation of Jak1, Tyk2, the insulin receptor substrate-1 and STAT6 respectively. These results suggest that STAT3 activation is involved with IL-4 and IL-13 signals in human B cells along with the activation of STAT6, and that there is a unique sequence in IL-13R1 to activate STAT3.
Keywords: B cell, Jak1, Jak3, STAT6
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. T. Avery, E. K. Deenick, C. S. Ma, S. Suryani, N. Simpson, G. Y. Chew, T. D. Chan, U. Palendira, J. Bustamante, S. Boisson-Dupuis, et al. B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans J. Exp. Med., January 18, 2010; 207(1): 155 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Jessup, A. W. Brewer, M. Omori, E. A. Rickel, A. L. Budelsky, B.-R. P. Yoon, S. F. Ziegler, and M. R. Comeau Intradermal Administration of Thymic Stromal Lymphopoietin Induces a T Cell- and Eosinophil-Dependent Systemic Th2 Inflammatory Response J. Immunol., September 15, 2008; 181(6): 4311 - 4319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Nakao, S. Kanaji, S. Ohta, H. Matsushita, K. Arima, N. Yuyama, M. Yamaya, K. Nakayama, H. Kubo, M. Watanabe, et al. Identification of Pendrin as a Common Mediator for Mucus Production in Bronchial Asthma and Chronic Obstructive Pulmonary Disease J. Immunol., May 1, 2008; 180(9): 6262 - 6269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Acacia de Sa Pinheiro, A. Morrot, S. Chakravarty, M. Overstreet, J. H. Bream, P. M. Irusta, and F. Zavala IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+ T cells J. Leukoc. Biol., April 1, 2007; 81(4): 1102 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Arguni, M. Arima, N. Tsuruoka, A. Sakamoto, M. Hatano, and T. Tokuhisa JunD/AP-1 and STAT3 are the major enhancer molecules for high Bcl6 expression in germinal center B cells Int. Immunol., July 1, 2006; 18(7): 1079 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Goda, T. Kanaji, S. Kanaji, G. Tanaka, K. Arima, S. Ohno, and K. Izuhara Involvement of IL-32 in activation-induced cell death in T cells Int. Immunol., February 1, 2006; 18(2): 233 - 240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Blancafort, E. I. Chen, B. Gonzalez, S. Bergquist, A. Zijlstra, D. Guthy, A. Brachat, R. H. Brakenhoff, J. P. Quigley, D. Erdmann, et al. Genetic reprogramming of tumor cells by zinc finger transcription factors PNAS, August 16, 2005; 102(33): 11716 - 11721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Arima, K. Sato, G. Tanaka, S. Kanaji, T. Terada, E. Honjo, R. Kuroki, Y. Matsuo, and K. Izuhara Characterization of the Interaction between Interleukin-13 and Interleukin-13 Receptors J. Biol. Chem., July 1, 2005; 280(26): 24915 - 24922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tanaka, S. Kanaji, A. Hirano, K. Arima, A. Shinagawa, C. Goda, S. Yasunaga, K. Ikizawa, Y. Yanagihara, M. Kubo, et al. Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells Int. Immunol., June 1, 2005; 17(6): 797 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. O. Rahaman, M. A. Vogelbaum, and S. J. Haque Aberrant Stat3 Signaling by Interleukin-4 in Malignant Glioma Cells: Involvement of IL-13R{alpha}2 Cancer Res., April 1, 2005; 65(7): 2956 - 2963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ek, C.-M. Hogerkorp, M. Dictor, M. Ehinger, and C. A. K. Borrebaeck Mantle Cell Lymphomas Express a Distinct Genetic Signature Affecting Lymphocyte Trafficking and Growth Regulation as Compared with Subpopulations of Normal Human B Cells Cancer Res., August 1, 2002; 62(15): 4398 - 4405. [Abstract] [Full Text] [PDF]
|
|