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 Methi, T. Articles by Tasken, K. Search for Related Content PubMed PubMed Citation Articles by Methi, T. Articles by Tasken, K.

Short-Interfering RNA-Mediated Lck Knockdown Results in Augmented Downstream T Cell Responses¹

The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway

The Src family kinase Lck is essential for T cell Ag receptor-mediated signaling. In this study, we report the effects of acute elimination of Lck in Jurkat TAg and primary T cells using RNA interference mediated by short-interfering RNAs. In cells with Lck knockdown (kd), proximal TCR signaling was strongly suppressed as indicated by reduced -chain phosphorylation and intracellular calcium mobilization. However, we observed sustained and elevated phosphorylation of ERK1/2 in Lck kd cells 30 min to 2 h after stimulation. Downstream effects on immune function as determined by activation of a NFAT-AP-1 reporter, and TCR/CD28-stimulated IL-2 secretion were strongly augmented in Jurkat and primary T cells, respectively. As expected, overexpression of SHP-1 in Jurkat cells inhibited TCR-induced NFAT-AP-1 activation, but this effect could be overcome by simultaneous kd of Lck. Furthermore, acute elimination of Lck also suppressed TCR-mediated activation of SHP-1, suggesting the possible role of SHP-1 in a negative feedback loop originating from Lck. This report underscores Lck as an important mediator of proximal TCR signaling, but also indicates a suppressive role on downstream immune function.

This article has been cited by other articles:

				T. Xu, L. Chen, X. Shang, L. Cui, J. Luo, C. Chen, X. Ba, and X. Zeng Critical role of Lck in L-selectin signaling induced by sulfatides engagement J. Leukoc. Biol., October 1, 2008; 84(4): 1192 - 1201. [Abstract] [Full Text] [PDF]

				X. Wang, L. Simeoni, J. A. Lindquist, J. Saez-Rodriguez, A. Ambach, E. D. Gilles, S. Kliche, and B. Schraven Dynamics of Proximal Signaling Events after TCR/CD8-Mediated Induction of Proliferation or Apoptosis in Mature CD8+ T Cells J. Immunol., May 15, 2008; 180(10): 6703 - 6712. [Abstract] [Full Text] [PDF]

				E. Merino, A. Avila-Flores, Y. Shirai, I. Moraga, N. Saito, and I. Merida Lck-Dependent Tyrosine Phosphorylation of Diacylglycerol Kinase {alpha} Regulates Its Membrane Association in T Cells J. Immunol., May 1, 2008; 180(9): 5805 - 5815. [Abstract] [Full Text] [PDF]

				S. Razani-Boroujerdi, R. T. Boyd, M. I. Davila-Garcia, J. S. Nandi, N. C. Mishra, S. P. Singh, J. C. Pena-Philippides, R. Langley, and M. L. Sopori T Cells Express {alpha}7-Nicotinic Acetylcholine Receptor Subunits That Require a Functional TCR and Leukocyte-Specific Protein Tyrosine Kinase for Nicotine-Induced Ca2+ Response J. Immunol., September 1, 2007; 179(5): 2889 - 2898. [Abstract] [Full Text] [PDF]

				D. Peter, S. L. C. Jin, M. Conti, A. Hatzelmann, and C. Zitt Differential Expression and Function of Phosphodiesterase 4 (PDE4) Subtypes in Human Primary CD4+ T Cells: Predominant Role of PDE4D J. Immunol., April 15, 2007; 178(8): 4820 - 4831. [Abstract] [Full Text] [PDF]