Characterization of IL-4 and IL-13 signals dependent on the human IL-13 receptor alpha chain 1: redundancy of requirement of tyrosine residue for STAT3 activation
| Autor: | Morimasa Wada, Mina Akaiwa, Ritsuko Umeshita-Suyama, Bin Yu, Kenji Izuhara, Koichi Nakajima, Kazuhiko Arima, Rie Sugimoto, Naotaka Hamasaki, Michihiko Kuwano |
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| Rok vydání: | 2000 |
| Předmět: |
STAT3 Transcription Factor
Immunology Lymphocyte Activation Transfection Receptor tyrosine kinase Cell Line Tumor Cells Cultured Immunology and Allergy Animals Humans Tyrosine Phosphorylation STAT3 Receptor Interleukin 4 TYK2 Kinase B-Lymphocytes Interleukin-13 biology Receptors Interleukin-13 Proteins General Medicine Janus Kinase 1 Receptors Interleukin Protein-Tyrosine Kinases Phosphoproteins Interleukin-13 Receptor alpha1 Subunit Cell biology DNA-Binding Proteins Enzyme Activation Insulin receptor Biochemistry Tyrosine kinase 2 Interleukin 13 COS Cells biology.protein Insulin Receptor Substrate Proteins Trans-Activators Interleukin-4 STAT6 Transcription Factor HeLa Cells Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0953-8178 |
| Popis: | IL-4 and IL-13 are pleiotropic cytokines whose biological activities overlap with each other. IL-13 receptor alpha chain 1 (IL-13R alpha 1) is necessary for binding to IL-13, and the heterodimer composed of IL-13R alpha 1 and IL-4R alpha chain transduces IL-13 and IL-4 signals; however, the functional mapping of the intracellular domain of IL-13R alpha 1 is not fully understood. In this study, we constructed wild and mutated types of human IL-13R alpha 1, and analyzed IL-4 and IL-13 signals using an IL-13R alpha 1-transfected human B cell line. Expression of IL-13R alpha 1 evoked STAT3 activation by IL-4 and IL-13, and in stimulated human B cells, on which IL-13R alpha 1 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-13R alpha 1 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-13R alpha 1 to activate STAT3. |
| Databáze: | OpenAIRE |
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