Activation of a ras-MAPK-dependent pathway by Epstein-Barr virus latent membrane protein 1 is essential for cellular transformation.
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.
Roberts
M L
ML
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Cooper
N R
NR
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology* / Q000821:virology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D014066:Palatine Tonsil; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014763:Viral Matrix Proteins / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins