The AKT pathway and key targets
Citations for Akt pathway targets
Akt is expressed as three isoforms: AKT1/ PKBα, AKT2/ PKBβ and AKT3/ PKBγ, respectively1. An amino terminal pleckstrin homology (PH) domain, a central serine–threonine catalytic domain, and a small carboxy‑terminal regulatory domain characterize all the three isoforms. The PH domain binds to phosphatidylinositol-3,4-bisphosphate (PIP2) and phosphatidylinositol-3,4,5-trisphosphate (PIP3), products of Phosphatidylinositol-4,5-bisphosphate 3-kinase ( PI3K. This binding causes Akt to locate to the plasma membrane, where it becomes phosphorylated by phosphoinositide-dependent kinase 1 (PDK1) on Thr308 in the activation loop of the catalytic domain. This phosphorylation leads to activation. Full activation requires phosphorylation at a second site (Ser473). Current evidence leads to the mTOR–rictor complex (mTORC2) as the primary kinase for the second phosphorylation event, although other kinases like Ilk (integrin linked kinase)2, PDK13. DNA-dependent protein kinase (DNA-PK)4, ATM (ataxia telangiectasia mutated) have also been identified5.
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