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 Bunin, A. Articles by Kersh, G. J. Search for Related Content PubMed PubMed Citation Articles by Bunin, A. Articles by Kersh, G. J.

Regulation of Bim by TCR Signals in CD4/CD8 Double-Positive Thymocytes¹

Anna Bunin^*, Fatima W. Khwaja and Gilbert J. Kersh^2,*

^* Department of Pathology and Laboratory Medicine and Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322

Bim, a BH3-only Bcl-2 family member, is required for apoptosis of thymocytes in response to negative selection signals. Regulation of the apoptotic activity of Bim during negative selection is not understood. In this study we demonstrate that in murine thymocytes undergoing apoptosis in response to anti-CD3 injection, levels of Bim protein expression do not change. In immature thymocytes, Bim is associated with mitochondria before stimulation and is not regulated by a change in subcellular localization during apoptosis. We also show that Bim_EL is rapidly phosphorylated in thymocytes in response to CD3 cross-linking both in vivo and in vitro, and that phosphorylation is sustained for at least 24 h. Analysis of MHC-deficient mice shows that phosphorylation of Bim occurs in CD4/CD8 double-positive thymocytes and does not depend on activation of mature T cells. We also find that TCR cross-linking on thymocytes induces an increase in the proportion of Bcl-x_L bound to Bim at late time points. Our results favor a model in which strong TCR signals regulate the apoptotic activity of Bim by phosphorylation and subsequent changes in binding to Bcl-x_L in immature thymocytes.

This article has been cited by other articles:

				J. Thompson and A. Winoto During negative selection, Nur77 family proteins translocate to mitochondria where they associate with Bcl-2 and expose its proapoptotic BH3 domain J. Exp. Med., May 12, 2008; 205(5): 1029 - 1036. [Abstract] [Full Text] [PDF]

				T. N. Jorgensen, A. McKee, M. Wang, E. Kushnir, J. White, Y. Refaeli, J. W. Kappler, and P. Marrack Bim and Bcl-2 Mutually Affect the Expression of the Other in T Cells J. Immunol., September 15, 2007; 179(6): 3417 - 3424. [Abstract] [Full Text] [PDF]

				T. A. Baldwin and K. A. Hogquist Transcriptional Analysis of Clonal Deletion In Vivo J. Immunol., July 15, 2007; 179(2): 837 - 844. [Abstract] [Full Text] [PDF]

				K. Cante-Barrett, E. M. Gallo, M. M. Winslow, and G. R. Crabtree Thymocyte Negative Selection Is Mediated by Protein Kinase C- and Ca2+-Dependent Transcriptional Induction of Bim J. Immunol., February 15, 2006; 176(4): 2299 - 2306. [Abstract] [Full Text] [PDF]