Control of Akt activity and substrate phosphorylation in cells

Protein kinase B/Akt is a serine/threonine kinase that links receptors coupled to the PI3K lipid kinase to cellular anabolic pathways. Its activity in cells is controlled by reversible phosphorylation and an intramolecular lipid‐controlled allosteric switch. In this review, I outline the current progress in understanding Akt regulatory mechanisms, define three models of Akt activation in cells, and highlight how intramolecular allosterism cooperates with cell‐autonomous mechanisms to control Akt localization and activity and direct it toward specific sets of substrates in cells.