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

Kathryn S. Campbell, Egon Ogris, Brenda Burke, Wen Su, Kurt R. Auger, Brian J. Druker, Brian S. Schaffhausen, Thomas M. Roberts, David C. Pallas

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166 Scopus citations

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-ProThr-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
StatePublished - Jul 5 1994

ASJC Scopus subject areas

  • General

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