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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raman, V. Articles by Chatila, T. A. Search for Related Content PubMed PubMed Citation Articles by Raman, V. Articles by Chatila, T. A.

Requirement for Ca²⁺/Calmodulin-Dependent Kinase Type IV/Gr in Setting the Thymocyte Selection Threshold¹

Vidya Raman^*, Frank Blaeser^*, Nga Ho^*, Deborah L. Engle^*, Calvin B. Williams^* and Talal A. Chatila^2,*,,

Departments of ^* Pediatrics and Pathology and Immunology and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110

The outcome of thymocyte selection is influenced by the nature of Ca²⁺ signals transduced by the TCR. Robust Ca²⁺ responses characterize high-affinity, negatively selecting peptide/TCR interactions, while modest responses typify lower-affinity, positively selecting interactions. To elucidate mechanisms by which thymocytes decode distinct Ca²⁺ signals, we examined selection events in mice lacking Ca²⁺/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr), which is enriched in thymocytes. CaMKIV/Gr-deficient thymocytes exhibited impaired positive selection and defective Ca²⁺-dependent gene transcription. Significantly, CaMKIV/Gr deficiency raised the selection threshold of peptide/TCR interactions such that a peptide that normally induced weak negative selection instead promoted positive selection. These results demonstrate an important role for CaMKIV/Gr in sensitizing thymocytes to selection by low-affinity peptides.

This article has been cited by other articles:

				B. Mellstrom, M. Savignac, R. Gomez-Villafuertes, and J. R. Naranjo Ca2+-Operated Transcriptional Networks: Molecular Mechanisms and In Vivo Models Physiol Rev, April 1, 2008; 88(2): 421 - 449. [Abstract] [Full Text] [PDF]

				M. Illario, M. L. Giardino-Torchia, U. Sankar, T. J. Ribar, M. Galgani, L. Vitiello, A. M. Masci, F. R. Bertani, E. Ciaglia, D. Astone, et al. Calmodulin-dependent kinase IV links Toll-like receptor 4 signaling with survival pathway of activated dendritic cells Blood, January 15, 2008; 111(2): 723 - 731. [Abstract] [Full Text] [PDF]

				K. A. Anderson, P. K. Noeldner, K. Reece, B. E. Wadzinski, and A. R. Means Regulation and Function of the Calcium/Calmodulin-dependent Protein Kinase IV/Protein Serine/Threonine Phosphatase 2A Signaling Complex J. Biol. Chem., July 23, 2004; 279(30): 31708 - 31716. [Abstract] [Full Text] [PDF]