Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-Kinase/Akt pathway.
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.
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Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
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D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology* / Q000637:transplantation / Q000821:virology; D002051:Burkitt Lymphoma / Q000473:pathology; D002461:Cell Line, Transformed; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D014763:Viral Matrix Proteins / Q000502:physiology*
D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D014763:Viral Matrix Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C494918:AKT1 protein, human