A human protein kinase Bγ with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain

We have cloned human protein kinase B gamma (PKB gamma) and found that it contains two regulatory phosphorylation sites, Thr(305) and Ser(472), which correspond to Thr(308) and Ser(473) Of PKB alpha. Thus it differs significantly from the previously published rat PKB gamma. We have also isolated a similar clone from a mouse cDNA library. In human tissues, PKB gamma is widely expressed as two transcripts. A mutational analysis of the two regulatory sites of human PKB gamma showed that phosphorylation of both sites, occurring in a phosphoinositide 3-kinase-dependent manner, is required for full activity. Our results suggest that the two phosphorylation sites act in concert to produce full activation of PKB gamma, similar to PKB alpha. This contrasts with rat PKB gamma, which is thought to be regulated by 3-phosphoinositide-dependent protein kinase 1 alone.