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