Abstract
Interaction with SV40 small tumor antigen (small t) compromised the ability of multimeric protein phosphatase 2A to inactivate the mitogen-activated protein kinase ERK1 and the mitogen-activated protein kinase kinase MEK1. Transient expression of small t in CV-1 cells activated MEK and ERK but did not affect Raf activity. Small t stimulated the growth of quiescent CV-1 cells almost as effectively as did serum. Coexpression of kinase-deficient ERK2 blocked most, but not all, of the proliferation caused by small t. Activation of the mitogen-activated protein kinase pathway and stimulation of cell growth were dependent on the interaction of small t with protein phosphatase 2A. These findings indicate that SV40 small t is capable of inducing cell growth through blockade of protein phosphatase and deregulation of the mitogen-activated protein kinase cascade.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Polyomavirus Transforming / physiology*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Cycle*
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Cell Line
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Chlorocebus aethiops
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Enzyme Activation
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinase Kinases*
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Mitogen-Activated Protein Kinases*
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Phosphoprotein Phosphatases / physiology*
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Protein Phosphatase 2
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-raf
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Transfection
Substances
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Antigens, Polyomavirus Transforming
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Proto-Oncogene Proteins
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases
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Phosphoprotein Phosphatases
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Protein Phosphatase 2