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  • Original Paper
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Association between src-kinases and the polyoma virus oncogene middle T-antigen requires PP2A and a specific sequence motif

Oncogene volume 18, pages 4364–4370 (1999)Cite this article

Abstract

Polyoma virus encodes a potent oncogene, the middle T-antigen (MT), that induces cell transformation by copying the actions of tyrosine kinase associated growth factor receptors. A crucial component of MT transformation is its ability to bind and stimulate the activity of src-family kinases. However, the mechanism by which this is achieved remains unclear. Tyrosine phosphorylation of MT by src-kinases then provides binding sites for SH2 and PTB domain containing molecules in a paradigm of receptor action. We present evidence here that the MT/src complex contains equi-molar amounts of PP2A, and that phosphatase activity may be required for the interaction of MT with both PP2A and the src-family. PP2A, then, is a necessary component of the MT-src complex. We also show that two motifs in the 185 to 210 region of MT, each consisting of a basic area followed by a serine or threonine, are essential for interaction with src-kinases, but not PP2A. The spacing between the serine or threonine and the basic sequence also appears to be important. Substituting a cysteine residue in place of Thr203 in MT has no affect on the binding of pp60c-src, showing that these sites interact with src-kinases by a novel mechanism that does not require phosphorylation.

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Acknowledgements

We would like to thank the many members of the ICSM who have helped with advice during the course of this work, particularly Dr Nina Krauzewicz and Dr Nick Dibb. This work was generously supported by a grant from the Cancer Research Campaign (UK).

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  1. Department of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK

    Hilary R Glover, Charlotte EP Brewster & Stephen M Dilworth

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Glover, H., Brewster, C. & Dilworth, S. Association between src-kinases and the polyoma virus oncogene middle T-antigen requires PP2A and a specific sequence motif. Oncogene 18, 4364–4370 (1999). https://doi.org/10.1038/sj.onc.1202816

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