Model outlining PTEN's involvement in signal transduction. PIP3 represents PtdIns-3,4,5-P3. Feedback modulation of insulin signaling by PTEN is shown. Expression of PTEN reduces the level of PtdIns-3,4,5-P3 in the cell, which leads to increased amounts of IRS-2 and an increased association with PI3K. Increased levels of PtdIns-3,4,5-P3 are associated with increased posttranslational modification of IRS-2 and disassociation with PI3K.