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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Amino Acid Sequence
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Animals
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Antigens, Polyomavirus Transforming / chemistry
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Antigens, Polyomavirus Transforming / isolation & purification
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Antigens, Polyomavirus Transforming / metabolism*
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Binding Sites
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Clone Cells
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ErbB Receptors / metabolism
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GRB2 Adaptor Protein
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Humans
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Mice
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Oncogene Proteins / chemistry
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Proteins / isolation & purification
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Proteins / metabolism*
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Proto-Oncogenes
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Sequence Homology, Amino Acid
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Shc Signaling Adaptor Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Antigens, Polyomavirus Transforming
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GRB2 Adaptor Protein
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GRB2 protein, human
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Grb2 protein, mouse
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Oncogene Proteins
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Proteins
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SHC1 protein, human
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Shc Signaling Adaptor Proteins
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Shc1 protein, mouse
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Src Homology 2 Domain-Containing, Transforming Protein 1
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ErbB Receptors