Serine/threonine-protein kinases SGK represent a kinase subfamily with orthologs found across animal clades and in yeast. In most vertebrates, including humans, there are three isoforms encoded by the genes SGK1, SGK2, and SGK3. The name Serum/glucocorticoid-regulated kinase refers to the first cloning of a SGK family member from a cDNA library screen for genes upregulated by the glucocorticoid dexamethasone in a rat mammary epithelial tumor cell line. The first human family member (human SGK1) was cloned in a screen of hepatocellular genes regulated in response to cellular hydration or swelling.
An Overview of SGK
Serum/glucocorticoid-regulated kinase (SGK) is a protein kinase belonging to the serine/threonine family, which is rapidly transcribed under a variety of stimuli including serum and glucocorticoids. SGK was originally isolated from the process of differentially screening for glucocorticoid-induced transcription in breast tumor cell lines. SGK is composed of an N-terminal (amino terminal), an intermediate catalytic domain, and a C-terminal (carboxy terminal). The SGK gene is 2.4 kb in length and encodes a protein with a relative molecular mass of 49 ku. SGK is widely expressed in animal tissues, with relatively high expression in ovarian, thymus and lung. SGK plays an important role in the interaction of many cell signal transduction pathways as well as the phosphorylation cascade of cells. In addition to being induced by glucocorticoids, serum, and mineralocorticoids, a variety of intracellular and extracellular factors can affect SGK transcription, activity, and intracellular localization. Thus, SGK plays a key role in signal transduction of ion channel, cell volume, cell survival, cell proliferation, and apoptosis.
Major type of SGK
The homologs of SGK include SGK1, SGK2, and SGK3. The similarity between the latter two and SGK1 is 80%, and the similarity at the C-terminus of the non-catalytic domain is 44% to 68%.
Inhibition of SGK
Currently, there are many SGK inhibitors that can be used to treat SGK-induced diseases such as diabetes, obesity, metabolic syndrome (lipeemia), systemic hypertension, cardiovascular disease and kidney disease. For example, EMD638683 is a highly selective SGK1 inhibitor and GSK 650394 is a novel SGK inhibitor. In the future, SGK may serve as a new therapeutic target for cancer.
SGK and diseases
Studies found that elevated levels of SGK mRNA in non-small cell lung cancer tissues was associated with clinical outcomes. The role of SGK in regulating ion channel is related to the absorption of pulmonary edema fluid. The regulation of SGK by transforming growth factor-β1 (TGF-β1) is associated with fibrotic diseases, and the role of SGK in pulmonary vascular remodeling is closely related to pulmonary hypertension. Therefore, SGK is associated with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) pulmonary fibrosis, pulmonary hypertension, and non-small cell lung cancer.
Lee, C.T., Tyan, S.W., Ma, Y.L., et al. () Serum- and glucocorticoid-inducible kinase (SGK) is a target of the MAPK/ERK signaling pathway that mediates memory formation in rats. Eur J Neurosci, 23(5): 1311-1320.