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The Journal of Immunology, 2000, 164: 1211-1215.
Copyright © 2000 by The American Association of Immunologists

Protein Tyrosine Phosphatase Activity Is Required for IL-4 Induction of IL-4 Receptor {alpha}-Chain

Hua Huang1 and William E. Paul2

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

To investigate the role of protein tyrosine phosphatases in IL-4R{alpha}-chain expression and signaling, we first established that SHP-1, but not SHP-2, coimmunoprecipitated with anti-IL-4R{alpha} 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-4R{alpha}-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-4R{alpha}-chain mRNA. The striking inhibition in total cellular IL-4R{alpha}-chain and in cell surface IL-4 receptors was associated with an inhibition of biosynthetic labeling of IL-4R{alpha}-chain after a 30- min pulse with [35S] methionine, indicating that reduction of IL-4R{alpha}-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-4R{alpha}-chain protein expression by phosphatase may provide a novel means to regulate IL-4 responsiveness.




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