Comprehensive analysis of the PTEN domains on TGFβ-induced aberrant cell motility in lung alveolar/epithelial cells by using PTEN constructs with deletion mutants

We recently showed that TGFβ-induced phosphorylation of the PTEN C-terminus might induce EMT and aberrant cell motility and that modulation of the PTEN C-terminus blocked these pathological phenotypes (Plos One 8(11):e81133.2013). But, we have not yet determined the exact mechanism, by which modulation of the PTEN C-terminus could show the inhibitory effect on aberrant cell motility. Therefore, this study is aimed to evaluate it, by using several PTEN constructs with deletion mutants. Four kinds of deletion mutants in the phosphatase domain, the C2 domain, and/or the PTEN C-terminus were prepared. And then, we established lung alveolar/epithelial cells with a Dox-dependent gene expression system, in which each these mutant is induced only when Dox is added. The effect of these PTEN constructs on TGFβ-induced cell aberrant motility was evaluated, by using migration assay. Migration assay suggested that both of the phosphatase and C2 domains might be essential to inhibit TGFβ-induced cell aberrant motility via the protein and lipid phosphatase activities. Furthermore, deletion of the PTEN C-terminus showed partial inhibition of the cell motility although the PTEN mutant retains the phosphatase activities. PTEN is newly classified as an intrinsically disordered protein (IDP) and the PTEN C-terminus is identified as the functional intrinsically disordered region that confers PTEN primary and secondary interactomes and dictates the majority of PTEN functions. Comprehensive analysis of PTEN as IDP gives us the new clue to control TGFβ-induced pathological phenotypes in lung alveolar/epithelial cells.