Engineering PTEN function: Membrane association and activity

Engineering PTEN function: membrane association and activity.

Many tumors are associated with deficiency of the tumor suppressor, PTEN, a PIP3 phosphatase that turns off PIP3 signaling. The major site of PTEN action is the plasma membrane, where PIP3 is produced by PI3 kinases. However, the mechanism and functional importance of PTEN membrane recruitment are poorly defined. Using the heterologous expression system in which human PTEN is expressed in Dicty...

Crystal Structure of the PTEN Tumor Suppressor Implications for Its Phosphoinositide Phosphatase Activity and Membrane Association

The PTEN tumor suppressor is mutated in diverse human cancers and in hereditary cancer predisposition syndromes. PTEN is a phosphatase that can act on both polypeptide and phosphoinositide substrates in vitro. The PTEN structure reveals a phosphatase domain that is similar to protein phosphatases but has an enlarged active site important for the accommodation of the phosphoinositide substrate. ...

A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN.

The PI 3-phosphatase PTEN (phosphatase and tensin homologue deleted on chromosome 10), one of the most important tumor suppressors, must associate with the plasma membrane to maintain appropriate steady-state levels of phosphatidylinositol 3,4,5-triphosphate. Yet the mechanism of membrane binding has received little attention and the key determinants that regulate localization, a phosphatidylin...

Membrane Engineering: Future Perspectives

Membrane Engineering for Today and for Tomorrow