Figure 1.

A model for the evolution of the PKB activating mechanisms. In ancestral eukaryotes lacking PH domain-containing PKB-like orthologues, interaction of PDK1 with PKB relied on the PIF-pocket mechanism. This promoted limited PKB activation that was responsible for essential functions such as supporting cell survival, a situation that is reproduced in the PDK1 K465E knock-in mice neurons. At the amoebozoans-metazoans origin, the acquisition of a PH domain allowed PKB to co-localize with PDK1 in response to PtdIns(3,4,5)P₃ raises. This enabled activating PKB with high efficiency, which allowed the recruitment of additional cellular substrates regulating novel functions, such as complex neuronal morphogenesis.