TY - JOUR
T1 - Protein phosphatase 2A isotypes regulate cell surface expression of the T cell receptor
AU - Lauritsen, Jens Peter Holst
AU - Menné, C
AU - Kastrup, J
AU - Dietrich, J
AU - Geisler, C
N1 - Keywords: Amino Acid Sequence; Antibiotics, Antifungal; Antigens, CD3; Down-Regulation; Endocytosis; Enzyme Inhibitors; Exocytosis; Humans; Isoenzymes; Jurkat Cells; Molecular Sequence Data; Okadaic Acid; Oxazoles; Phosphoprotein Phosphatases; Phosphorylation; Protein Phosphatase 2; Pyrans; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, gamma-delta; Receptors, Transferrin; Spiro Compounds
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 11150850
SN - 0254-9670
VL - 18
SP - 24
EP - 33
JO - Experimental and Clinical Immunogenetics
JF - Experimental and Clinical Immunogenetics
IS - 1
ER -