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

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Peng-Pilon, M. Articles by Brodin, P. Search for Related Content PubMed PubMed Citation Articles by Peng-Pilon, M. Articles by Brodin, P. Agricola Articles by Peng-Pilon, M. Articles by Brodin, P.

The cytoplasmic C-terminal domain but not the N-terminal domain of latent membrane protein 1 of Epstein—Barr virus is essential for B cell activation

Marc Peng-Pilon

Department of Cell and Molecular Biology, University of Umeå, Umeå S-901 87, Sweden

The Epstein—Barr virus (EBV) latent membrane protein 1 (LMP-1) is essential for EBV-induced immortalization of human primary B cells, transforms rodent fibroblasts and induces the up-regulation of several B cell activation markers when transiently expressed in primary B cells. The biochemical function of LMP-1 is unclear and limited information is available on the involvement of different domains of the protein in B cell activation. The present study describes the characterization of LMP-1 N- and C-terminal deletion mutants in terms of their cell surface distribution and ability to induce activation markers in primary human B cells and in the type I Burkitt's lymphoma cell line DG75. The C-terminal deletion mutant was detected by immunofluorescence via antibodies targeted against an eight amino acid FLAG epitope substituted for the entire predicted cytoplasmic C-terminal domain. Our findings show that N-terminal deletion mutants of LMP-1 are unable to attain their usual patched distribution on the plasma membrane but retain the ability to activate B cells. In contrast, the C-terminal deletion mutant shows the same patched cell surface distribution as wild-type LMP-1 but is unable to activate B cells. The patched distribution of LMP-1 in the plasma membrane is therefore not sufficient nor necessary for the induction of B cell activation and the results rule out patching as a direct mechanism in LMP-1-induced activation. This is the first study addressing the role of the LMP-1 C-terminal domain in lymphocytes and our results show that this domain is essential for B cell activation and therefore likely to be important for the early events of B cell immortalization by EBV.

Present address: Department of Molecular and Cellular Biology, Life Sciences Addition, University of California at Berkeley, Berkeley, CA 94720, USA.

^* Author for correspondence. Fax +46 90 111420. e-mail Peter.Brodin@CMB.UMU.Se

Received 6 July 1994; accepted 21 November 1994.

This article has been cited by other articles:

				M. M. Brinkmann and T. F. Schulz Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. J. Gen. Virol., May 1, 2006; 87(Pt 5): 1047 - 1074. [Abstract] [Full Text] [PDF]

				K. D. Brown, B. S. Hostager, and G. A. Bishop Differential Signaling and Tumor Necrosis Factor Receptor-associated Factor (TRAF) Degradation Mediated by CD40 and the Epstein-Barr Virus Oncoprotein Latent Membrane Protein 1 (LMP1) J. Exp. Med., April 16, 2001; 193(8): 943 - 954. [Abstract] [Full Text] [PDF]