Mutation of a cysteine residue in polyomavirus middle T antigen abolishes interactions with protein phosphatase 2A, pp60c-src, and phosphatidylinositol-3 kinase, activation of c-fos expression, and cellular transformation.
Polyomavirus middle T antigen (MT) interacts with several cellular proteins involved in cell proliferation. MT forms complexes with protein phosphatase 2A (PP2A), pp60c-src (and the related kinases c-fyn and c-yes), and phosphatidylinositol-3 kinase. We made a single point mutation in MT, changing a conserved cysteine residue at position 120 to tryptophan, and characterized the biochemical and biological properties of the mutant (C120W) protein. The mutant MT protein does not associate with PP2A, pp60c-src, or phosphatidylinositol-3 kinase as judged by coimmunoprecipitation and associated phosphatase or kinase activity. The C120W mutant is defective in activation of c-fos expression and in morphological transformation of NIH 3T3 cells.
Glenn
G M
GM
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186-5800.
Eckhart
W
W
D019870:1-Phosphatidylinositol 4-Kinase; D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D003545:Cysteine / Q000737:chemistry; D015967:Gene Expression Regulation, Viral; D016762:Genes, fos; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism*; D011120:Polyomavirus / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054648:Protein Phosphatase 2; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000952:Antigens, Polyomavirus Transforming; D046911:Macromolecular Substances; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D016392:Proto-Oncogene Proteins pp60(c-src); D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D003545:Cysteine