PDK1 phosphoinositide-dependent protein kinase

Alessi, D.R., Deak, M., Casamayor, A., Caudwell, F.B., Morrice, N., Norman, D.G., Gaffney, P., Reese, C.B., MacDougall, C.N., Harbison, D., et al. (1997). 3-Phosphoinositide-dependent protein kinase-1 (PDK1) structural and functional homology with the Drosophila DSTPK61 kinase. Curr Biol 7, 776-789. 

Activation of Akt kinase proceeds in a multi-step process with regulation by PtdIns(3,4,5)P3 as the critical step. PtdIns(3,4,5)P3 binds to the PH domain of Akt kinase and thereby recruits the enzyme to the cell membrane. This step is thought to be a prerequisite for a subsequent phosphorylation of a Thr residue in the activation loop (see Chapter 7 on protein kinases) and an N-terminal Ser residue of Akt. The protein kinase responsible for this step is named phosphoinositide-dependent protein kinase 1 (PDK1, review Vanhaesebroeck and Alessi, 2000), and this also contains a PH domain with high affinity for PtdIns(3,4,5)P3. Membrane targeting and the double phosphorylation activate Akt, allowing the phosphorylation of downstream substrates like the Bad protein (see Section 15.7.1), pro-caspase 9, the transription factor CREB (see Section 1.4.5.2), glycogen synthase kinase (GSK), and 6-phosphofructo-2-kinase. 

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