Research ArticleCancer

PTEN Protein Phosphatase Activity Correlates with Control of Gene Expression and Invasion, a Tumor-Suppressing Phenotype, But Not with AKT Activity

Sci. Signal.  28 Feb 2012:
Vol. 5, Issue 213, pp. ra18
DOI: 10.1126/scisignal.2002138

You are currently viewing the editor's summary.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Self-Directed Phosphatase

The 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 PTEN’s 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 PTEN’s 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 PTEN’s 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 AKT’s phosphorylation and catalytic activity but lacked protein phosphatase activity and failed to suppress invasion, suggesting that PTEN’s protein phosphatase activity may contribute to its tumor suppressor function.