The function of Akt (protein kinase B) is regulated by phosphorylation on two sites conserved
within the AGC kinase family: the activation loop (Thr-308) in the kinase core and a
hydrophobic phosphorylation site on the carboxyl terminus (Ser-473). Thr-308 is
phosphorylated by the phosphoinositide-dependent kinase-1,(PDK-1), whereas the
mechanism of phosphorylation of the hydrophobic site, tentatively referred to as the PDK-2
site, is unknown. Here we report that phosphorylation of the hydrophobic motif requires …