The PHLPP isoforms (PH domain and Leucine rich repeat Protein Phosphatases) are a pair of protein phosphatases, PHLPP1 and PHLPP2, that are important regulators of Akt serine-threonine kinases (Akt1, Akt2, Akt3) and conventional/novel protein kinase C (PKC) isoforms. PHLPP may act as a tumor suppressor in several types of cancer due to its ability to block growth factor-induced signaling in cancer cells.
PHLPP dephosphorylates Ser-473 (the hydrophobic motif) in Akt, thus partially inactivating the kinase.
In addition, PHLPP dephosphorylates conventional and novel members of the protein kinase C family at their hydrophobic motifs, corresponding to Ser-660 in PKCβII.