PTEN (gene)

Phosphatase and tensin homolog (PTEN) is a protein that, in humans, is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers. PTEN orthologs have been identified in most mammals for which complete genome data are available.

This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin-like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating Akt/PKB signaling pathway.

Function

The PTEN protein is widely expressed throughout the body. PTEN protein acts as a phosphatase to dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P₃ or PIP₃). PTEN specifically catalyses the dephosporylation of the 3` phosphate of the inositol ring in PIP₃, resulting in the biphosphate product PIP₂ (PtdIns(4,5)P2). This dephosphorylation is important because it results in inhibition of the AKT signaling pathway.