text: The phosphatases in the PHLPP family, PHLPP1 and PHLPP2 have been shown to directly dephosphorylate, and therefore inactivate, distinct Akt isoforms, at one of the two critical phosphorylation sites required for activation: Serine473.  PHLPP2 dephosphorylates AKT1 and AKT3, whereas PHLPP1 is specific for AKT2 and AKT3.  Lack of PHLPP appears to have  effects on growth factor-induced Akt phosphorylation.  When both PHLPP1 and PHLPP2 are knocked down using siRNA and cells are stimulated using epidermal growth factor, peak Akt phosphorylation at both Serine473 and Threonine308 (the other site required for full Akt activation) is increased dramatically.