Polyoma virus middle t-antigen: growth factor receptor mimic

Nicholson, Philippa R.; Dilworth, S. J.

doi:10.1016/s0168-7069(01)05004-2

Cited by 2 publications

(1 citation statement)

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“…The middle T‐antigen (MT) encoded by the murine polyomavirus is a potent oncogene that can fully transform established rodent fibroblasts in one step. It achieves this by interacting with a series of host polypeptides and altering their normal regulation (reviewed in Dilworth, 1995; Nicholson and Dilworth, 2001). In a series of interactions, MT binds first to the A and C subunits of protein phosphatase 2A (PP2A), and then associates with one of the src ‐family of tyrosine kinases, pp60 c‐src , pp59 c‐fyn or pp62 c‐yes , which stimulates tyrosine kinase activity.…”

Section: Introductionmentioning

confidence: 99%

ShcA tyrosine phosphorylation sites can replace ShcA binding in signalling by middle T-antigen

et al. 2001

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ShcA and Grb2 are crucial components in signalling by most tyrosine kinase‐associated receptors. How ever, it is not clear whether Grb2 bound directly to the receptor is equivalent to Grb2 associated via ShcA. We have used signalling stimulated by the middle T‐antigen (MT) of polyoma virus to address this question. The two known Grb2‐binding sites from murine ShcA, 313Y and 239/240YY, could functionally replace the MT ShcA‐interacting region in transformation assays using Rat2 fibroblasts. This demonstrates that signal output from membrane‐bound ShcA requires only these two sequences and the ShcA‐binding site in MT does not recruit other signalling molecules. Two standard Grb2‐interacting sequences, either from the EGF receptor or the ShcA 313Y region, could not replace the requirement for ShcA binding to MT, indicating an enhanced role for the ShcA 239/240YY motif. Sos1 and the docking protein Gab1 are brought into the MT complex through Grb2 association and this may be more effective using the 239/240YY sequence.

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Section: Introductionmentioning

confidence: 99%