Campbell K S, Ogris E, Burke B, Su W, Auger K R, Druker B J, Schaffhausen B S, Roberts T M, Pallas D C
Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6344-8. doi: 10.1073/pnas.91.14.6344.
Polyomavirus middle tumor antigen (MT) transforms a large number of cell types by binding to and modulating the activities of cellular proteins. Previous genetic analysis defined in MT an independent motif, NPTY (Asn-Pro-Thr-Tyr), required for transformation. This report demonstrates that NPTY is required for interaction between MT and SHC protein, a Src homology 2 (SH2)-containing protooncogene product implicated in activating Ras via association with GRB2 protein. SHC is phosphorylated on tyrosine and associates with GRB2 in MT-transformed cells. These effects require an intact NPTY motif in MT. SHC immunoprecipitates from MT-transformed cells possess kinase activity that phosphorylates not only SHC and MT but also the 85-kDa subunit of phosphatidylinositol 3-kinase. This result suggests that a complex exists that contains, at a minimum, MT, Src family tyrosine kinases, phosphatidylinositol 3-kinase, and SHC.
