Abstract
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.
MeSH terms
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Animals
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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COS Cells
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Cell Line
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DNA-Binding Proteins / metabolism*
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Enzyme Activation / immunology
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HeLa Cells
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Humans
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Insulin Receptor Substrate Proteins
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Interleukin-13 / metabolism
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Interleukin-13 / physiology*
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Interleukin-13 Receptor alpha1 Subunit
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Interleukin-4 / physiology*
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Janus Kinase 1
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Lymphocyte Activation
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Phosphoproteins / genetics
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Phosphoproteins / physiology
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Phosphorylation
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Protein-Tyrosine Kinases / metabolism
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Proteins / metabolism
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin / genetics
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Receptors, Interleukin / physiology*
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Receptors, Interleukin-13
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STAT3 Transcription Factor
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STAT6 Transcription Factor
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Signal Transduction / genetics
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Signal Transduction / immunology*
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TYK2 Kinase
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Trans-Activators / metabolism*
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Trans-Activators / physiology
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Transfection
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Tumor Cells, Cultured
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Tyrosine / metabolism
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Tyrosine / physiology*
Substances
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DNA-Binding Proteins
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IL13RA1 protein, human
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IRS1 protein, human
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Insulin Receptor Substrate Proteins
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Interleukin-13
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Interleukin-13 Receptor alpha1 Subunit
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Phosphoproteins
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Proteins
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Receptors, Interleukin
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Receptors, Interleukin-13
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STAT3 Transcription Factor
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STAT3 protein, human
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STAT6 Transcription Factor
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STAT6 protein, human
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Trans-Activators
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Interleukin-4
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Tyrosine
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Protein-Tyrosine Kinases
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JAK1 protein, human
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Janus Kinase 1
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TYK2 Kinase
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TYK2 protein, human