Protein phosphatase 2A isotypes regulate cell surface expression of the T cell receptor

The mechanisms underlying T cell receptor (TCR) down-regulation have been e xtensively studied during the last decade, Whereas the importance of phosph orylation in this process has been established, it is less certain whether dephosphorylation plays a role in TCR down-regulation. In this study, we sh ow that inhibition of the serine/threonine protein phosphatase PP2A family had a biphasic effect on TCR expression. Thus, low concentrations of PP2A i nhibitors induced TCR down-regulation, whereas higher concentrations of PP2 A inhibitors induced TCR up-regulation, The effect of PP2A inhibition was i ndependent of phosphorylation of the CD3 gamma endocytosis motif. Whereas T CR down-regulation was caused by a partial inhibition of exocytosis, TCR up -regulation was caused by an inhibition of endocytosis, The effects on exoc ytosis and endocytosis were not restricted to the ICR, indicating a more ge neral regulatory role for PP2A in both exocytosis and endocytosis. Copyrigh t (C) 2001 S. Karger AG. Basel.