HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bauler, T. J. Articles by King, P. D. Search for Related Content PubMed PubMed Citation Articles by Bauler, T. J. Articles by King, P. D.

Normal TCR Signal Transduction in Mice That Lack Catalytically Active PTPN3 Protein Tyrosine Phosphatase¹

Timothy J. Bauler^*, Elizabeth D. Hughes, Yutaka Arimura, Tomas Mustelin, Thomas L. Saunders^, and Philip D. King^2,*

^* Department of Microbiology and Immunology, Transgenic Animal Model Core, and Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, MI 48109; and Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, La Jolla, CA 92037

PTPN3 (PTPH1) is a cytoskeletal protein tyrosine phosphatase that has been implicated as a negative regulator of early TCR signal transduction and T cell activation. To determine whether PTPN3 functions as a physiological negative regulator of TCR signaling in primary T cells, we generated gene-trapped and gene-targeted mouse strains that lack expression of catalytically active PTPN3. PTPN3 phosphatase-negative mice were born in expected Mendelian ratios and exhibited normal growth and development. Furthermore, numbers and ratios of T cells in primary and secondary lymphoid organs were unaffected by the PTPN3 mutations and there were no signs of spontaneous T cell activation in the mutant mice with increasing age. TCR-induced signal transduction, cytokine production, and proliferation was normal in PTPN3 phosphatase-negative mice. This was observed using both quiescent T cells and recently stimulated T cells where expression of PTPN3 is substantially up-regulated. We conclude, therefore, that the phosphatase activity of PTPN3 is dispensable for negative regulation of TCR signal transduction and T cell activation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by American Heart Association Grant 0555597Z and by National Institutes of Health National Research Service Award 5-T32-GM07544 from the National Institute of General Medical Sciences.

² Address correspondence and reprint requests to Dr. Philip D. King, Department of Microbiology and Immunology, University of Michigan Medical School, 6606 Medical Science II, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0620. E-mail address: kingp{at}umich.edu

³ Abbreviations used in this paper: PTK, protein tyrosine kinase; PTP, protein tyrosine phosphatase; SHP-1, Src homology region 2 domain-containing phosphatase 1; ES, embryonic stem; Neo^R, neomycin resistance; LN, lymph node; DN, double-negative thymocyte; SEB, staphylococcal enterotoxin B; TACE, TNF--convertase; VCP, Valosin-containing protein; PEP, PEST-domain phosphatase.

This article has been cited by other articles:

				I. Pilecka, C. Patrignani, R. Pescini, M.-L. Curchod, D. Perrin, Y. Xue, J. Yasenchak, A. Clark, M. C. Magnone, P. Zaratin, et al. Protein-tyrosine Phosphatase H1 Controls Growth Hormone Receptor Signaling and Systemic Growth J. Biol. Chem., November 30, 2007; 282(48): 35405 - 35415. [Abstract] [Full Text] [PDF]