Polyoma middle tumor antigen interacts with SHC protein via the NPTY (Asn- Pro-Thr-Tyr) motif in middle tumor antigen

K. S. Campbell, E. Ogris, B. Burke, W. Su, K. R. Auger, B. J. Druker, B. S. Schaffhausen, T. M. Roberts, D. C. Pallas

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)6344-6348
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number14
DOIs
StatePublished - 1994

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