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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 Cgamma 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 Cgamma 1 (PLCgamma 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 PLCgamma 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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