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.
Baker
J E
JE
Department of Medicine and the Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143-0795, USA.
Majeti
R
R
Tangye
S G
SG
Weiss
A
A
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D019169:Jurkat Cells; D008565:Membrane Proteins; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D007527:Isoenzymes; C110810:LAT protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; C486288:PTPRJ protein, human; D017027:Protein Tyrosine Phosphatases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D010738:Type C Phospholipases; D051966:Phospholipase C gamma