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 CD3gamma 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 TCR, indicating a more general regulatory role for PP2A in both exocytosis and endocytosis.
Lauritsen
J P
JP
Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark.
Menné
C
C
Kastrup
J
J
Dietrich
J
J
Geisler
C
C
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology; D017252:CD3 Complex / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D019169:Jurkat Cells; D008387:Marine Toxins; D008969:Molecular Sequence Data; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D011714:Pyrans; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D013141:Spiro Compounds
D000935:Antifungal Agents; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008387:Marine Toxins; D010080:Oxazoles; D011714:Pyrans; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011990:Receptors, Transferrin; D013141:Spiro Compounds; C053079:tautomycin; D019319:Okadaic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2