THE INTERACTION OF SV40 SMALL TUMOR-ANTIGEN WITH PROTEIN PHOSPHATASE-2A STIMULATES THE MAP KINASE PATHWAY AND INDUCES CELL-PROLIFERATION

Interaction with SV40 small tumor antigen (small t) compromised the ab ility of multimeric protein phosphatase 2A to inactivate the mitogen-a ctivated protein kinase ERK1 and the mitogen-activated protein kinase kinase MEK1. Transient expression of small t in CV-1 cells activated M EK and ERK but did not affect Raf activity. Small t stimulated the gro wth of quiescent CV-1 cells almost as effectively as did serum. Coexpr ession of kinase-deficient ERK2 blocked most, but not all, of the prol iferation caused by small t. Activation of the mitogen-activated prote in kinase pathway and stimulation of cell growth were dependent on the interaction of small t with protein phosphatase 2A. These findings in dicate that SV40 small t is capable of inducing cell growth through bl ockade of protein phosphatase and deregulation of the mitogen-activate d protein kinase cascade.