Abstract
The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is the only EBV protein which possesses the properties of an oncogene. In studies initiated to evaluate the mechanisms involved in EBV-induced malignant transformation, the extracellular response kinase (ERK) 1/2 were found to be activated 2 days after EBV infection of purified resting human B cells. Transfection studies in Rat-1 fibroblasts, an established rodent cell line, showed that LMP1 mediates ERK 1/2 activation. Cotransfection experiments with a dominant negative ras mutant demonstrated that such MAPK activation occurs via a ras-dependent pathway. Finally, cotransfection studies showed that ras activation is required for LMP-1-mediated malignant transformation of Rat-1 cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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B-Lymphocytes / immunology
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B-Lymphocytes / physiology*
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B-Lymphocytes / virology*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Transformation, Neoplastic*
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Herpesvirus 4, Human / physiology*
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Humans
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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Oncogene Proteins, Viral / metabolism*
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Palatine Tonsil
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Rats
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Recombinant Proteins / metabolism
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Signal Transduction
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Transfection
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Viral Matrix Proteins / metabolism*
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ras Proteins / metabolism*
Substances
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EBV-associated membrane antigen, Epstein-Barr virus
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Oncogene Proteins, Viral
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Recombinant Proteins
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Viral Matrix Proteins
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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ras Proteins