Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase C gamma 1 phosphorylation

In this study, we investigate the role of the receptor-like protein tyrosin e phosphatase CD148 in T-cell activation, Overexpression of CD148 in the Ju rkat T-cell line inhibited activation of the transcription factor nuclear f actor of activated T cells following T-cell receptor (TCR) stimulation but not following stimulation through a heterologously expressed G protein-coup led receptor, the human muscarinic receptor subtype 1. Using a tetracycline -inducible expression system, we show that the TCR-mediated activation of b oth the Ras and calcium pathways was inhibited by expression of CD148 at le vels that approximate those found in activated primary T cells. These effec ts were dependent on the phosphatase activity of CD148. Analysis of TCR-ind uced protein tyrosine phosphorylation demonstrated that most phosphoprotein s were unaffected by CD148 expression. However, phospholipase C gamma1 (PLC gamma1) and LAT were strikingly hypophosphorylated in CD148-expressing cel ls following TCR stimulation, whereas the phosphorylation levels of SIp-76 and Itk were modestly reduced. Based on these results, we propose that CD14 8 negatively regulates TCR signaling by interfering with the phosphorylatio n and function of PLC gamma1 and LAT.