Abstract
A mutation in the human (hu) IL-4R alpha, Q576R, has been linked with allergy in humans. Increased sensitivity of patients cells with this mutation to IL-4 suggest that a Q576R change enhances IL-4 signaling. To directly test this hypothesis, we analyzed the ability of huIL-4R alpha cDNA bearing the Q576R and Y575F mutations to signal tyrosine phosphorylation, DNA-binding activity, proliferation, protection from apoptosis, and CD23 induction in response to huIL-4 in murine cells. Responses generated by the Q576R and Y575F mutants were similar to those of the wild-type receptor, using various concentrations of huIL-4 and times of stimulation. These results indicate that neither the Q576R nor the Y575F mutations have a significant direct effect on IL-4 signal transduction, and that hypersensitive induction of CD23 in cells derived from human allergy patients may be due to different and/or additional alterations in the IL-4 signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Substitution / genetics
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Amino Acid Substitution / immunology
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Animals
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Apoptosis / genetics
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Apoptosis / immunology
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Arginine / genetics
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Cell Line
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DNA-Binding Proteins / biosynthesis
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Glutamine / genetics
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Humans
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Hypersensitivity / genetics*
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Hypersensitivity / immunology
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Insulin Receptor Substrate Proteins
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Lymphocyte Activation / genetics
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Mice
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Mutagenesis, Site-Directed / immunology*
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Phosphoproteins / metabolism
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Phosphorylation
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Receptor, Insulin / metabolism
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Receptors, IgE / biosynthesis
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Receptors, Interleukin-4 / genetics*
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Receptors, Interleukin-4 / physiology
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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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Trans-Activators / metabolism
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Tyrosine / genetics
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Tyrosine / metabolism
Substances
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DNA-Binding Proteins
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IRS1 protein, human
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Insulin Receptor Substrate Proteins
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Irs1 protein, mouse
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Phosphoproteins
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Receptors, IgE
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Receptors, Interleukin-4
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STAT6 Transcription Factor
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STAT6 protein, human
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Stat6 protein, mouse
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Trans-Activators
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Glutamine
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Tyrosine
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Arginine
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Receptor, Insulin