Both lipid- and protein-phosphatase activities of PTEN contribute to the p53-PTEN anti-invasion pathway.

Jacquelyne S Poon, Robert Eves, Alan S Mak

Department of Biochemistry, Kingston, ON, Canada.

Cell cycle (Georgetown, Tex.) 2010 Nov 15

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We have recently identified mutually antagonizing signaling pathways that regulate podosome formation and invasive phenotypes in Src-transformed vascular smooth muscle cells and fibroblasts. Cross-talks between the anti-invasion p53-PTEN, and the pro-invasion Src-Stat3 and Src-PI3K-Akt pathways serve as a check and balance that dictates the outcome of either an invasive or non-invasive phenotype. Using a retrovirus vector encoding PTEN phosphatase mutants that retain either protein- or lipid-phosphatase activity on a Src(Y527F)background, we report here that both lipid- and protein-phosphatase activities of PTEN contribute to the suppression of Src-induced podosome formation and associated invasive phenotypes in rat aortic smooth muscle cells. This data suggests that p53 up-regulation of PTEN inhibits cell invasion via a two-prong mechanism: inactivating podosome agonists by its protein-phosphatase activity on the one hand, and antagonising the PI3K-Akt pathway by its lipid-phosphatase activity on the other.

Citation

Jacquelyne S Poon, Robert Eves, Alan S Mak. Both lipid- and protein-phosphatase activities of PTEN contribute to the p53-PTEN anti-invasion pathway. Cell cycle (Georgetown, Tex.). 2010 Nov 15;9(22):4450-4