InterPro domain: IPR045101

This entry represents the phosphatase domain found in PTEN, which is a magnesium-dependent bifunctional phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase/dual-specificity protein phosphatase PTEN ( 3.1.3.67 ; 3.1.3.16 ; 3.1.3.48 ), which possesses the following catalytic activities:

• Phosphatidylinositol 3,4,5-trisphosphate + H(2)O = phosphatidylinositol 4,5-bisphosphate + phosphate.
• A phosphoprotein + H(2)O = a protein + phosphate.
• Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.

This protein acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins [ 1 ]. It also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate. The lipid phosphatase activity is critical for its tumour suppressor function [ 2 ]. PTEN antagonizes the PI3K-AKT/PKB signalling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form of PTEN cooperates with AIP1 to suppress AKT1 activation. PTEN dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion form [ 3 ].

1. PTEN catalysis of phospholipid dephosphorylation reaction follows a two-step mechanism in which the conserved aspartate-92 does not function as the general acid--mechanistic analysis of a familial Cowden disease-associated PTEN mutation. Cell. Signal. 19, 1434-45
2. PTEN: a new guardian of the genome. Oncogene 27, 5443-53
3. Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J. Cell Biol. 183, 101-16