The protein kinase Akt is activated in the PI3K pathway by a combination of signaling phospholipids and phosphorylation by upstream protein kinases. However, their respective contributions to the activity of Akt in the cell remains controversial. The lab of Thomas Leonard has determined the first high-resolution structure of near full-length Akt1 without the use of pharmacological inhibitors. Their findings provide new insights into how signaling lipids limit the spatial activity of Akt to membranes. The study, published in PNAS, also reveals the mechanistic basis of how Akt is perturbed in cancer and in Proteus syndrome, a rare overgrowth disease.
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