Enzyme inhibitor
This tumor-suppressing, Mg2+-dependent dual-specificity protein phosphatase (MW = 47166 g/mol; GenBank: AAD13528.1), which catalyzes the dephosphorylation of phosphotyrosine-, phosphoserine- and phosphothreonine-containing proteins, is also a lipid phosphatase (Reaction: Phosphatidylinositol 3,4,5-trisphosphate + H2O Phosphatidylinositol 4,5-bisphosphate + Pi), with the following in vitro substrate preference: PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. PTEN antagonizes PI3K-AKT/PKB signaling by dephosphorylating phosphoinositides and reduces cell cycle progression and survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. PTEN catalyzes the dephosphorylation of tyrosine-phosphorylated focal adhesion kinase, inhibiting cell migration and integrin-mediated cell spreading. PTEN also modulates AKT-mTOR signaling. PTEN plays an essential role in the maintenance of genome stability. PTEN also dephosphorylates MCM2 and inhibits replication fork progression under replication stress, suggesting that PTEN is involved in an S-phase checkpoint. DNA molecular combing analysis revealed that replication forks in PTEN-proficient cells are subject to more efficient braking in response to fork stalling than the forks in PTEN-deficient cells.
