SGK

Serum- and glucocorticoid-inducible kinases (SGKs) form a novel family of serine/threonine kinases that are activated in response to a variety of extracellular stimuli. SGK family contains three isoforms: SGK1, SGK2, and SGK3. The mRNA encoding SGK1, the best-studied member of the SGK family, is rapidly induced in response to a variety of stimuli, including growth factors, steroid and peptide hormones, cytokines, changes in cell volume, and brain injury.

SGKs are related to Akt (also called PKB), a serine/threonine kinase that plays a crucial role in promoting cell survival. The SGK family members share similar structure, substrate specificity and function with AKT and signal downstream of the phosphatidylinositol 3-kinase (PI3K) signalling pathway. They regulate a range of fundamental cellular processes such as cell proliferation and survival, thereby playing an important role in cancer development. In addition, SGKs not only regulate cell proliferation and survival, but also play important roles in cancer development via an AKT-independent signalling pathway. The importance of SGKs in cancer development and the scarcity of potent and selective SGK inhibitors support the urgent need for discovery and development of small molecules inhibitors targeting SGK for PIK3CA mutant cancers, and especially those that are resistant to AKT inhibition.