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
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