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

J. Biol. Chem., Vol. 281, Issue 43, 32385-32394, October 27, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/43/32385    most recent M604878200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Wood, J. E. Articles by Rudd, C. E. Search for Related Content PubMed PubMed Citation Articles by Wood, J. E. Articles by Rudd, C. E. Social Bookmarking                      What's this?

TcR and TcR-CD28 Engagement of Protein Kinase B (PKB/AKT) and Glycogen Synthase Kinase-3 (GSK-3) Operates Independently of Guanine Nucleotide Exchange Factor VAV-1^*

Joanne E. Wood, Helga Schneider, and Christopher E. Rudd¹

From the Molecular Immunology Section, Department of Immunology, Imperial College London, London W12 ONN, United Kingdom and the Cell Signalling Section, Division of Immunology, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 IQP, United Kingdom

TcR/CD3 and TcR/CD3-CD28 signaling requires the guanine nucleotide exchange factor (GEF) Vav-1 as well as the activation of phosphatidylinositol 3-kinase, protein kinase B (PKB/AKT), and its inactivation of glycogen synthase kinase-3 (GSK-3). Whether these two pathways are connected or operate independently of each other in T-cells has been unclear. Here, we report that anti-CD3 and anti-CD3/CD28 can induce PKB and GSK-3 phosphorylation in the Vav-1^–/– Jurkat cell line J. Vav.1 and in primary CD4-positive Vav-1^–/– T-cells. Reduced GSK-3 phosphorylation was observed in Vav-1,2,3^–/– T-cells together with a complete loss of FOXO1 phosphorylation. Furthermore, PKB and GSK-3 phosphorylation was unperturbed in the presence of GEF-inactive Vav-1 that inhibited interleukin-2 gene activation and a form of Src homology 2 domain-containing lymphocytic protein of 76-kDa (SLP-76) that is defective in binding to Vav-1. The pathway also was intact under conditions of c-Jun N-terminal kinase (JNK) inhibition and disruption of the actin cytoskeleton by cytochalasin D. Both events are down-stream targets of Vav-1. Overall, our findings indicate that the TcR and TcR-CD28 driven PKB-GSK-3 pathway can operate independently of Vav-1 in T-cells.

Received for publication, May 22, 2006

^* This work was supported by a grant from the Wellcome Trust, London. 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 Recipient of a Principal Research Fellow Award. To whom correspondence should be addressed. Tel.: 44-1223-765-661; Fax: 44-1223-764-733; E-mail: cer51{at}cam.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. F. Dodson, J. S. Boomer, C. M. Deppong, D. D. Shah, J. Sim, T. L. Bricker, J. H. Russell, and J. M. Green Targeted Knock-In Mice Expressing Mutations of CD28 Reveal an Essential Pathway for Costimulation Mol. Cell. Biol., July 1, 2009; 29(13): 3710 - 3721. [Abstract] [Full Text] [PDF]

				C. A. Garcia, M. R. Benakanakere, P. Alard, M. M. Kosiewicz, D. F. Kinane, and M. Martin Antigenic Experience Dictates Functional Role of Glycogen Synthase Kinase-3 in Human CD4+ T Cell Responses J. Immunol., December 15, 2008; 181(12): 8363 - 8371. [Abstract] [Full Text] [PDF]

				B. Wei, S. da Rocha Dias, H. Wang, and C. E. Rudd CTL-Associated Antigen-4 Ligation Induces Rapid T Cell Polarization That Depends on Phosphatidylinositol 3-Kinase, Vav-1, Cdc42, and Myosin Light Chain Kinase J. Immunol., July 1, 2007; 179(1): 400 - 408. [Abstract] [Full Text] [PDF]