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Journal of Virology, November 2000, p. 10838-10845, Vol. 74, No. 22
Department of Microbiology-Immunology,
Northwestern University Medical School, Chicago, Illinois
606111; Program in Viral Oncogenesis
and Tumor Immunology, Department of Virology and Molecular Biology,
St. Jude Children's Research Hospital, Memphis, Tennessee
381052; and Department of Pathology,
University of Tennessee Health Sciences Center, Memphis, Tennessee
381633
Received 30 May 2000/Accepted 23 August 2000
Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is
expressed on the membranes of B lymphocytes and blocks B-cell receptor
(BCR) signaling in EBV-transformed B lymphocytes in vitro. The
phosphotyrosine motifs at positions 74 or 85 and 112 within the LMP2A
amino-terminal domain are essential for the LMP2A-mediated block of
B-cell signal transduction. In vivo studies indicate that LMP2A allows
B-cell survival in the absence of normal BCR signals. A possible role
for Akt in the LMP2A-mediated B-cell survival was investigated. The
protein kinase Akt is a crucial regulator of cell survival and is
activated within B lymphocytes upon BCR cross-linking. LMP2A expression
resulted in the constitutive phosphorylation of Akt, and this LMP2A
effect is dependent on phosphatidylinositol 3-kinase activity. In
addition, recruitment of Syk and Lyn protein tyrosine kinases (PTKs) to
tyrosines 74 or 85 and 112, respectively, are critical for
LMP2A-mediated Akt phosphorylation. However, the ability of LMP2A to
mediate a survival phenotype downstream of Akt could not be detected in
EBV-negative Akata cells. This would indicate that LMP2A is not
responsible for EBV-dependent Burkitt's lymphoma cell survival.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Latent Membrane Protein 2A-Mediated Effects on the
Phosphatidylinositol 3-Kinase/Akt Pathway
*
Corresponding author. Mailing address: Department of
Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Phone: (312) 503-0467. Fax: (312)
503-1339. E-mail: r-longnecker{at}northwestern.edu.
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