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 Lin, M. Y. Articles by Hedrick, S. M. Search for Related Content PubMed PubMed Citation Articles by Lin, M. Y. Articles by Hedrick, S. M.

A Pivotal Role for the Multifunctional Calcium/Calmodulin-Dependent Protein Kinase II in T Cells: From Activation to Unresponsiveness¹

Meei Yun Lin^2,*, Tomasz Zal, Irene L. Ch’en^*, Nicholas R. J. Gascoigne and Stephen M. Hedrick^3,*

^* Division of Biological Sciences, The Cancer Center, and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093; and Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

Stimulation of the TCR leads to an oscillatory release of free calcium that activates members of the calcium/calmodulin-dependent protein kinase II (CaMKII) family. The CaMKII molecules have profound and lasting effects on cellular signaling in several cell types, yet the role of CaMKII in T cells is still poorly characterized. In this report we describe a splice variant of CaMKII, CaMKII'e, in mouse T cells. We have determined its function, along with that of CaMKII, by introducing the active and kinase-dead mutants into activated P14 TCR transgenic T cells using retroviral transduction. Active CaMKII enhanced the proliferation and cytotoxic activity of T cells while reducing their IL-2 production. Furthermore, it induced a profound state of unresponsiveness that could be overcome only by prolonged culture in IL-2. These results indicate that members of the CaMKII family play an important role in regulation of CD8 T cell proliferation, cytotoxic effector function, and the response to restimulation.

This article has been cited by other articles:

				X. Liu, M. Yao, N. Li, C. Wang, Y. Zheng, and X. Cao CaMKII promotes TLR-triggered proinflammatory cytokine and type I interferon production by directly binding and activating TAK1 and IRF3 in macrophages Blood, December 15, 2008; 112(13): 4961 - 4970. [Abstract] [Full Text] [PDF]

				I. L. Ch'en, D. R. Beisner, A. Degterev, C. Lynch, J. Yuan, A. Hoffmann, and S. M. Hedrick Antigen-mediated T cell expansion regulated by parallel pathways of death PNAS, November 11, 2008; 105(45): 17463 - 17468. [Abstract] [Full Text] [PDF]

				L.-F. Lee, C.-J. Lih, C.-J. Huang, T. Cao, S. N. Cohen, and H. O. McDevitt Genomic expression profiling of TNF-{alpha}-treated BDC2.5 diabetogenic CD4+ T cells PNAS, July 22, 2008; 105(29): 10107 - 10112. [Abstract] [Full Text] [PDF]

				J. Si and S. J. Collins Activated Ca2+/Calmodulin-Dependent Protein Kinase II{gamma} Is a Critical Regulator of Myeloid Leukemia Cell Proliferation Cancer Res., May 15, 2008; 68(10): 3733 - 3742. [Abstract] [Full Text] [PDF]

				P. Tamas, S. A. Hawley, R. G. Clarke, K. J. Mustard, K. Green, D. G. Hardie, and D. A. Cantrell Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes J. Exp. Med., July 10, 2006; 203(7): 1665 - 1670. [Abstract] [Full Text] [PDF]

				A. Bosco, K. L. McKenna, C. J. Devitt, M. J. Firth, P. D. Sly, and P. G. Holt Identification of novel th2-associated genes in T memory responses to allergens. J. Immunol., April 15, 2006; 176(8): 4766 - 4777. [Abstract] [Full Text] [PDF]