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

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