title: Both lipid- and protein-phosphatase activities of PTEN contribute to the p53-PTEN anti-invasion pathway.
abstract: 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.
authors.affiliation: Department of Biochemistry, Kingston, ON, Canada.
authors.forename: Jacquelyne S
authors.initials: JS
authors.lastname: Poon
authors.forename: Robert
authors.initials: R
authors.lastname: Eves
authors.forename: Alan S
authors.initials: AS
authors.lastname: Mak
mesh_terms: D000818:Animals; D002465:Cell Movement; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase