PHLPP: A Phosphatase that Directly Dephosphorylates Akt, Promotes Apoptosis, and Suppresses Tumor Growth

摘要: Akt/protein kinase B critically regulates the balance between cell survival and apoptosis. Phosphorylation of Akt at two key sites, activation loop hydrophobic motif, activates promotes survival. The mechanism dephosphorylation signal termination is unknown. Here, we identify a protein phosphatase, PH domain leucine-rich repeat phosphatase (PHLPP), that specifically dephosphorylates motif (Ser473 in Akt1), triggering apoptosis suppressing tumor growth. effects PHLPP on are prevented cells expressing an S473D construct Akt, revealing primary cellular target PHLPP. levels markedly reduced several colon cancer glioblastoma lines have elevated phosphorylation. Reintroduction into line causes dramatic suppression These data consistent with terminating signaling by directly dephosphorylating inactivating Akt.