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PTEN is a tumor suppressor gene. Recombinant PTEN is capable of dephosphorylating phosphatidylinositol 3,4,5-triphosphate[PI(3,4,5)P3], the product of phosphatidylinositol 3 -kinase. Many of the cancer-related mutations have been mapped to the phosphatase catalytic domain, it has been suggested that the phosphatase activity of PTEN is required for its tumor suppressor function. The activation of PKB/AKT is regulated in a complex manner via phosphorylation of AKT on Thr308 and Ser473 by PDK1 and ILK(integrin-linked kinase) respectively. Inactivation of PTEN will constitutively activate PKB/AKT pathway. In addition to its role in regulating the PI 3-K/AKT cell survival pathway, PTEN also inhibits growth factor-induced Shc phosphorylation and suppresses the mitogen-activated protein (MAP) kinase signaling pathway. PTEN also interact with FAK, a key molecule implicated in integrin signaling pathways, and it directly dephosphorylates tyrosine-phosphorylated FAK. PTEN down-regulation of p130CAS through FAK results in inhibition of cell migration and spreading. |
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