Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation.

In this study, we investigate the role of the receptor-like protein tyrosine phosphatase CD148 in T-cell activation. Overexpression of CD148 in the Jurkat T-cell line inhibited activation of the transcription factor nuclear factor of activated T cells following T-cell receptor (TCR) stimulation but not following stimulation through a heterologously expressed ...
G protein-coupled receptor, the human muscarinic receptor subtype 1. Using a tetracycline-inducible expression system, we show that the TCR-mediated activation of both the Ras and calcium pathways was inhibited by expression of CD148 at levels that approximate those found in activated primary T cells. These effects were dependent on the phosphatase activity of CD148. Analysis of TCR-induced protein tyrosine phosphorylation demonstrated that most phosphoproteins were unaffected by CD148 expression. However, phospholipase Cgamma1 (PLCgamma1) and LAT were strikingly hypophosphorylated in CD148-expressing cells following TCR stimulation, whereas the phosphorylation levels of Slp-76 and Itk were modestly reduced. Based on these results, we propose that CD148 negatively regulates TCR signaling by interfering with the phosphorylation and function of PLCgamma1 and LAT.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Carrier Proteins, Humans, Isoenzymes, Jurkat Cells, Membrane Proteins, Phospholipase C gamma, Phosphoproteins, Phosphorylation, Protein Tyrosine Phosphatases, Receptor-Like Protein Tyrosine Phosphatases, Class 3, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Type C Phospholipases
Mol. Cell. Biol.
Date: Apr. 01, 2001
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