PKB alpha (AKT1) is one of three closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) which may be alternatively named PKB α, PKB β, and PKB γ, respectively. Together, they regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (Kumar et al., 2013). Cloning of the gene was first described by Staal et al. (1987). PKB alpha is a member of the most frequently activated proliferation and survival pathway in cancer. The activation of PKB alpha is driven by membrane localization, which is in turn initiated by the binding of the pleckstrin homology (PH) domain to phosphatidylinositol-3,4,5-trisphosphate or phosphatidylinositol-3,4- bisphosphate, followed by phosphorylation of the regulatory amino acids serine 473 (Ser-473) and threonine 308 (Thr-308) on PKB alpha (Kumar and Purohit, 2013). PKB alpha seems to have a crucial but passive role in oncogenesis and acts as an indirect intermediary between mutated upstream regulatory proteins and downstream signalling molecules (Kumar and Purohit, 2013). PKB alpha is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation (Rena et al., 1999). Unregulated activation of the PKB pathway is a prominent feature of many human cancers and PKB alpha is overexpressed or activated in all major cancers. For these reasons, PKB alpha is considered an attractive target for cancer therapy (Wang et al., 2011).

References:

Kumar A and Purohit R (2013) Cancer associated E17K mutation causes rapid conformational drift in AKT1 pleckstrin homology (PH) domain. PLoS One 8, e64364.

Kumar A, Rajendran V, Sethumadhavan R and Purohit R (2013) AKT kinase pathway: a leading target in cancer research. Scientific World Journal 2013, 756134.

Rena G, Guo S, Cichy SC, Unterman TG and Cohen P (1999) Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J Biol Chem 274, 17179-17183.

Staal SP (1987) Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A 84, 5034-5037.

Wang P, Zhang L, Hao Q and Zhao G (2011) Developments in selective small molecule ATP-targeting the serine/threonine kinase Akt/PKB. Mini Rev Med Chem 11, 1093-1107.