PTEN (phosphatase and tensin homologue deleted on chromosome ten) is a dual-specificity phosphatase (with both protein and lipid phosphatase activity) first identified as a tumor suppressor gene. PTEN indirectly activates the AKT/PI3K pathway, an important signaling pathway for cell growth and proliferation by keeping levels of the second messenger PIP3 low, thereby preventing phosphoinositide-dependent kinase-1 (PDK-1) from phosphorylating and activating AKT. Expression of wild-type PTEN causes growth arrest in many cancer cell lines, but expression of a PTEN protein containing a mutation that blocks its lipid phosphatase activity failed to suppress growth of glioma cell lines suggesting that the tumor suppressive effect of PTEN is mediated solely by its lipid phosphatase activity. Other activities include the inhibition of insulin stimulated MAPK activation by blocking the insulin-receptor substrate (IRS)-1 phosphorylation and assembly of the IRS-1/Grb2/Sos complex.
