PerspectiveCell Signaling

Proline hydroxylation linked to Akt activation

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Science  26 Aug 2016:
Vol. 353, Issue 6302, pp. 870-871
DOI: 10.1126/science.aah6254


  • Shutting down Akt

    Upon growth factor stimulation, Akt is recruited to the cell membrane by the actions of PI3K, where it is activated by phosphorylation (P) by other membrane-associated kinases such as 3-phosphoinositide-dependent protein kinase-1 (PDK1). Phosphorylated Akt1 and Akt2, but not Akt3, undergo proline hydroxylation (OH) by the prolyl hydroxylase EglN1 under conditions of normal oxygen tension. Hydroxylated Akt interacts with, and is dephosphorylated by, pVHL-associated PP2A, leading to Akt inactivation. Ptdins(4,5), phosphatidylinositol 4,5-bisphosphate; Ptdins(3,4,5), phosphatidylinositol 3,4,5-triphosphate; mTORC2, mTOR complex 2.


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