PKBα is composed of three main domains:
In its inactive state, PKBα resides in the cytosol. Upon cellular stimulation, such as through insulin or growth factors, phosphoinositide 3-kinase (PI3K) generates lipid products that recruit PKBα to the plasma membrane. Here, PKBα undergoes phosphorylation at two key residues: Thr308 in the kinase domain and Ser473 in the regulatory domain. This phosphorylation fully activates PKBα, enabling it to phosphorylate downstream targets .
PKBα is a major mediator of the cellular responses to insulin and insulin-like growth factor 1 (IGF1). It plays a pivotal role in:
PKBα is implicated in various diseases, particularly cancer. Its role in promoting cell survival and growth makes it a key player in tumorigenesis. Overactivation of PKBα is often observed in cancers, where it contributes to uncontrolled cell proliferation and resistance to apoptosis . Additionally, PKBα has been linked to metabolic disorders such as diabetes, due to its critical role in insulin signaling .
Recombinant human PKBα is produced using various expression systems, including baculovirus-insect cells. The recombinant protein is typically purified and formulated for use in research and therapeutic applications. It is used to study the biochemical properties of PKBα, screen for potential inhibitors, and understand its role in various signaling pathways .