Abstract
To investigate the role of protein tyrosine phosphatases in IL-4Ralpha-chain expression and signaling, we first established that SHP-1, but not SHP-2, coimmunoprecipitated with anti-IL-4Ralpha chain Abs in extracts prepared from resting lymphocytes. We further observed that the protein tyrosine phosphatase inhibitors Na3VO4 and pervanadate blocked the striking induction of IL-4Ralpha-chain expression that is mediated by IL-4. However, Na3VO4 did not diminish IL-4-induced Stat6 phosphorylation nor did it block the IL-4-mediated increase in IL-4Ralpha-chain mRNA. The striking inhibition in total cellular IL-4Ralpha-chain and in cell surface IL-4 receptors was associated with an inhibition of biosynthetic labeling of IL-4Ralpha-chain after a 30- min pulse with [35S] methionine, indicating that reduction of IL-4Ralpha-chain protein resulted from either a diminished production of the receptor or a rapid degradation, possibly as a result of phosphorylation of the receptor in an early biosynthetic cellular compartment. Control of newly synthesized IL-4Ralpha-chain protein expression by phosphatase may provide a novel means to regulate IL-4 responsiveness.
MeSH terms
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Animals
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Cells, Cultured
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Enzyme Activation / immunology
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Interleukin-4 / metabolism
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Interleukin-4 / physiology*
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Intracellular Signaling Peptides and Proteins
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Lymph Nodes / cytology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / metabolism*
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RNA, Messenger / biosynthesis
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Receptors, Interleukin-4 / antagonists & inhibitors
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Receptors, Interleukin-4 / biosynthesis*
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Receptors, Interleukin-4 / genetics
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SH2 Domain-Containing Protein Tyrosine Phosphatases
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STAT6 Transcription Factor
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Signal Transduction / immunology
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Spleen / cytology
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Trans-Activators / metabolism
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Trans-Activators / physiology
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Vanadates / pharmacology
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src Homology Domains / immunology
Substances
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Intracellular Signaling Peptides and Proteins
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RNA, Messenger
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Receptors, Interleukin-4
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STAT6 Transcription Factor
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Stat6 protein, mouse
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Trans-Activators
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Interleukin-4
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Vanadates
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Ptpn11 protein, mouse
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Ptpn6 protein, mouse
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SH2 Domain-Containing Protein Tyrosine Phosphatases