Abstract

PKB belongs to the large set of related AGC kinases having a preference for phosphorylating basophilic sites. Protein kinase B (PKB/Akt/Rac-protein kinase) is a key player in the signaling pathways of numerous essential eukaryotic cellular processes including glucose metabolism, cell proliferation, apoptosis, cell migration and transcription. Many targets of PKB have been identified in vitro, and many studies looking at in vivo roles are currently underway.

Kinase activity of PKB is stimulated by a variety of growth factors, cytokines, chemokines, heat shock, hyperosmolarity, hypoxia, integrin engagement and T-cell receptor interactions.

The N-termini of the protein contains a plectrin homology (PH) domain which binds lipid products of phosphoinositide 3'-kinase (PI3K) and mediates recruitment to the membrane in response to PI3K (10945990). Translocation of PKB then allows phosphorylation at Thr-308 by another Ser/Thr protein kinase (3-phosphoinositide-dependent protein kinase 1 (PDK1)) and full activation occurs after phosphorylation of Ser-473, by an as yet unidentified kinase, or by autophosphorylation (10722653). A serine (or less often a threonine) residue at the end of the motif in PKB substrates is then phosphorylated.