AMINO-TERMINAL REGIONS OF POLYOMAVIRUS MIDDLE T-ANTIGEN ARE REQUIRED FOR INTERACTIONS WITH PROTEIN PHOSPHATASE 2A

Polyomavirus middle T antigen (MT) is the major transforming protein of the virus. It functions through interactions with a number of cellular proteins involved in cell proliferation, MT forms complexes with protein phosphatase 2A (PP2A), pp60(c-src), phosphatidylinositol 3-kinase, and She. We introduced both deletion and point mutations into three regions of MT and examined their ability to associate with PP2A and pp60(c-src). The first 25 amino acid residues of MT are required for association with PP2A and pp60(c-src). Amino acids 105 to 111, comprising the sequence Cys-Arg-Met-Pro-Leu-Thr-Cys, is also required for complex formation between MT and PP2A. However, the sequence Asp-Lys-Gly-Gly (amino acids 44 to 47), also found in the B subunit of PP2A, is dispensable for complex formation between MT and PP2A. We find a strict correlation between the ability of MT to associate with PP2A and the ability of MT to associate with pp60(c-src). One mutant, L5E, associates with a phosphatase other than PP2A,pp60(c-src) and phosphatidylinositol 3-kinase in a manner similar to that of wild-type MT yet is reduced in its transforming ability on NIH 3T3 cells.