Sci. Signal., 28 February 2012
Self-Directed PhosphataseThe lipid and protein phosphatase PTEN, which acts as a tumor suppressor, is known for its ability to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate and thereby antagonize mitogenic signaling by phosphoinositide 3-kinase and downstream effectors, such as AKT. The role of PTENs protein phosphatase activity, however, is less clear. Tibarewal et al. used PTEN mutants to isolate its protein phosphatase activity from its lipid phosphatase activity and found that both appeared to be required on the same molecule for PTEN to inhibit glioma cell invasion in vitro. In addition, both its lipid and its protein phosphatase activities were required to mediate many of PTENs largest effects on gene expression. Various lines of evidence indicated that PTEN dephosphorylated a residue in its own C-terminal tail and implicated dephosphorylation of this residue in limiting invasion independently of any effects on AKT, leading the authors to propose that autodephosphorylation may enable targeting PTENs lipid phosphatase activity to a particular locale. The authors identified a PTEN mutant from a human lung cancer cell line that retained the ability to decrease AKTs phosphorylation and catalytic activity but lacked protein phosphatase activity and failed to suppress invasion, suggesting that PTENs protein phosphatase activity may contribute to its tumor suppressor function.
Citation: P. Tibarewal, G. Zilidis, L. Spinelli, N. Schurch, H. Maccario, A. Gray, N. M. Perera, L. Davidson, G. J. Barton, N. R. Leslie, PTEN Protein Phosphatase Activity Correlates with Control of Gene Expression and Invasion, a Tumor-Suppressing Phenotype, But Not with AKT Activity. Sci. Signal. 5, ra18 (2012).
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