Transformation by polyoma virus middle T-antigen involves the binding and tyrosine phosphorylation of Shc

Stephen M. Dilworth, Charlotte E P Brewster, Michael D. Jones, Luisa Lanfrancone, Gulliana Pelicci, Pier G. Pelicci

Research output: Contribution to journalArticle

Abstract

Polyoma virus middle T-antigen converts normal fibroblasts to a fully transformed, tumorigenic phenotype. It achieves this, at least in part, by binding and activating one of the non-receptor tyrosine kinases, pp60(c- src), pp62(c-yes) or pp59(c-fyn) (reviewed in refs 2 and 3). As a result, middle T-antigen itself is phosphorylated on tyrosine residues, one of which (Tyr 315) acts as a binding site for the SH2 domains of phosphatidylinositol- 3'OH kinase 85K subunit. Here we show that another tyrosine phosphorylation site in middle T-antigen (Tyr 250; refs 4, 5) acts as a binding region for the SH2 domain of the transforming protein Shc9. This results in Shc also becoming tyrosine-phosphorylated and binding to the SH2 domain of Grb2 (ref. 10). This probably stimulates p21(ras) activity through the mammalian homologue of the Drosophila guanine-nucleotide-exchange factor Sos (reviewed in ref. 11). We suggest that middle T-antigen transforms cells by acting as a functional homologue of an activated tyrosine kinase-associated growth- factor receptor.

Original languageEnglish
Pages (from-to)87-90
Number of pages4
JournalNature
Volume367
Issue number6458
DOIs
Publication statusPublished - Jan 6 1994

ASJC Scopus subject areas

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