SGK is a serine-threonine protein kinase with high homology to second messengers such as PKB/Akt. The full name is serum and glucocorticoid induced kinase. In addition to similar phosphorylation-dephosphorylation regulation to most protein kinases that have been discovered, SGK is also regulated by the rapid transcription phase. It may serve as a functional meeting point for a variety of cellular signaling links and cellular phosphorylation-dephosphorylation cascades. It is widely believed that SGK is involved in the transmission of sodium channel regulatory signals, cell proliferation signals, and cell survival signals.

Figure 1. Structure of protein SGK1.

Introductions

The serine/threonine protein kinase SGK represents a subfamily of kinases found in animal clade and yeast. In most vertebrates, including humans, there are three isoforms encoded by the genes SGK1, SGK2, and SGK3. The name of serum / glucocorticoid-regulated kinase refers to the gene for which glucocorticoid dexamethasone was up-regulated in a rat mammary epithelial tumor cell line of SGK family members for the first time cloned from a cDNA library screen. The first human family member (human SGK1) was cloned into a hepatocyte gene screen that was regulated in response to cellular hydration or swelling. The term SGK is also used as a synonym for SGK1.

Functions

Among these three SGK genes, the research on SGK1 gene is the most in-depth. This gene encodes a serine/threonine protein kinase that is highly similar to rat serum and glucocorticoid-induced protein kinase (SGK). The gene was identified in a hepatocyte gene screen that is regulated in response to cell hydration or swelling. Cell hydration is a catabolism signal that stimulates glycogen breakdown and proteolysis, and inhibits protein and glycogen synthesis. This kinase has been shown to be important in activating certain potassium, sodium and chlorine channels. The expression of this gene in hepatocytes is stimulated by transforming growth factor-beta (TGF-beta), which is involved in the pathophysiology of diabetes complications. The increased expression of TGF-β and SGK in diabetic nephropathy suggests that SGK is involved in the development of the disease. SGK1 kinase regulates inositol transporters during osmotic stress. Imbalanced expression of SGK1 in endometrium may be related to human infertility or repeated abortion, and the expression of SGK1 in endometrium may also affect fertility in mice.

1. Cell volume regulation

SGK1 is upregulated by osmotic and isotonic cell contraction. It is easy to speculate that the regulation of SGK1-dependent cation channels helps to regulate cell volume, which involves cation channels in various cells. The entry of NaCl and osmotic water into cells results in an increase in cell regulatory cell volume. This occurs because the entry of Na + polarizes the cell and therefore allows Cl- to enter in parallel. SGK1 has also been shown to increase cell volume-regulated Cl-channel ClC2 activity. Activation of these Cl-channels results in the presence of Cl- and ultimately K +, while the loss of KCl cells results in a decrease in regulatory cell volume.

2. Cell proliferation and apoptosis

SGK1 has been shown to inhibit apoptosis. It is suggested that the proliferation signal transports SGK1 into the nucleus. The effect of SGK1 on cell proliferation may be due to its ability to regulate Kv1.3. SGK1 is not a key factor in regulating cell proliferation or apoptosis, or related kinases can effectively replace SGK1 function in SGK1 knockout microphones.

3. Transcription

The human isoform of SGK1 has been identified as a cell volume-regulating gene whose transcription is upregulated through cell contraction. The regulation of SGK1 transcription levels is fast; the appearance and disappearance of SGK1 mRNA takes <20 minutes. Its transcription is increasingly expressed by serum and glucocorticoids, and transcriptional changes in SGK1 expression are related to the appearance of cell death Signal molecules involved in the regulation of SGK1 transcription include cAMP, p53, and protein kinase C. Since SGK1 transcription is sensitive to cell volume, the expression of SGK1 in the brain is upregulated by dehydration.

Role in neuronal diseases

The two major components of SGK1 expression, namely oxidative stress and increased glucocorticoids, are common components of the neurodegenerative process. AMPA and heinate receptors are regulated by the SGK subtype. AMPA receptor activation is key to ischemia-induced cell death. In the case of observed changes in GluR2 levels, it has been shown that SGK1-dependent AMPA and kainic acid receptor regulatory disorders may be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), schizophrenia. And epilepsy. The alginate receptor is thought to be involved in epilepsy activity. The glutamate transporter functions to remove glutamate from extracellular space. Lack of SGK1 may prevent glutamate activity while reducing glutamate clearance from the synaptic cleft. Because glutamate may exert neurotoxic effects, altering the function or regulation of glutamate transporters and glutamate receptors may promote neuroexcitatory toxicity.

References

1. Saha, M; et al. Rsk phosphorylation of SOS1 negatively regulates MAPK activation. The Biochemical Journal. 2012, 447 (1): 159-66.
2. Lang F; et al. Significance of SGK1 in the regulation of neuronal function. The Journal of Physiology. 2010, 588 (Pt 18): 3349-3354.