MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baker, J. E.
Right arrow Articles by Weiss, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baker, J. E.
Right arrow Articles by Weiss, A.

 Previous Article  |  Next Article 

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.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2001 by the American Society for Microbiology. All rights reserved.