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Molecular and Cellular Biology, April 2001, p. 2393-2403, Vol. 21, No. 7
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.7.2393-2403.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Protein Tyrosine Phosphatase CD148-Mediated Inhibition of T-Cell
Receptor Signal Transduction Is Associated with Reduced LAT and
Phospholipase C
1 Phosphorylation
Jeanne E.
Baker,1
Ravindra
Majeti,1
Stuart G.
Tangye,2 and
Arthur
Weiss1,*
Departments of Medicine and of Microbiology
and Immunology and the Howard Hughes Medical Institute, University
of California, San Francisco, San Francisco, California
94143-0795,1 and Centenary Institute
of Cancer Medicine and Cell Biology, New South Wales,
Australia2
Received 18 September 2000/Returned for modification 20 November
2000/Accepted 5 January 2001
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 C
1 (PLC
1) 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 PLC
1 and LAT.
*
Corresponding author. Mailing address: Departments of
Medicine and of Microbiology and Immunology and the Howard Hughes
Medical Institute, University of California, San Francisco, 3rd and
Parnassus Ave., San Francisco, CA 94143-0795. Phone: (415) 476-1291. Fax: (415) 502-5081. E-mail: aweiss{at}medicine.ucsf.edu.
Molecular and Cellular Biology, April 2001, p. 2393-2403, Vol. 21, No. 7
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.7.2393-2403.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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