Protein tyrosine phosphatase activity is required for IL-4 induction of IL-4 receptor alpha-chain

To investigate the role of protein tyrosine phosphatases in IL-4R alpha-cha in 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 ph osphatase inhibitors Na3VO4 and pervanadate blocked the striking induction of IL-4R alpha-chain expression that is mediated by IL-4. However, Na3VO4 d id 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 t otal cellular IL-4R alpha-chain and in cell surface IL-4 receptors was asso ciated with an inhibition of biosynthetic labeling of IL-4R alpha-chain aft er a 30- min pulse with [S-35] 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 new ly synthesized IL-4R alpha-chain protein expression by phosphatase may prov ide a novel means to regulate IL-4 responsiveness.