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. Serine / threonine protein kinases phosphorylate OH groups of serine or threonine (with similar side chains). The activity of these protein kinases can be regulated by specific events (such as DNA damage) and many chemical signals, including cAMP/cGMP, diacylglycerol, and Ca²⁺/calmodulin. A very important group of protein kinases are MAP kinases. Important subgroups are kinases of the ERK subfamily (usually activated by mitotic signals), and stress-activated protein kinases JNK and p38. Although MAP kinases are serine/threonine specific, they are activated by the combined phosphorylation of serine/threonine and tyrosine residues. The activity of MAP kinases is limited by many protein phosphatases that remove phosphate groups added to specific serine or threonine residues of the kinase, which are necessary to maintain the kinase in its active conformation. Two main factors affecting MAP kinase activity: a) the signal to activate transmembrane receptors (natural ligands or cross-linking agents) and the proteins associated with them (mutations that mimic active states) b) the phosphate that limits a given MAP kinase Signal of enzyme inactivation. These signals include oxidative stress.

Figure 1. Calcium/calmodulin-dependent protein kinase II (CaMKII) is an example of a serine/threonine-specific protein kinase.

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.

YANK family

YANK family belongs to the protein kinase superfamily. Ser/Thr protein kinase family. 3 alternatively spliced human isoforms have been reported.

Figure 2. Protein structure of YANK family.

YANK2

STK32B or YANK2 is a serine/threonine protein kinase that contains a motif that binds metal ions and nucleotides, and the STK32B gene is highly conserved among various species. STK32B has been associated with isolated left cleft, with or without pa cleft and c cleft, which is the most common birth defect in patients with oral cleft palate. Long-dispersed nuclear element 1 (LINE-1 or L1) -mediated deletion of the STK32B gene was observed in patients with borderline intelligence in Ellis-van Creveld syndrome.

YANK3

STK32C or YANK3 is a member of the YANK family. It is a serine / threonine protein kinase of about 486aa and requires magnesium to exert its catalytic activity. There are two isoforms of the protein produced by alternative splicing, and the protein undergoes serine phosphorylation by upstream protein kinases. The STK32C gene product is preserved in many species, including chimpanzees, dogs, cattle, mice, rats and chickens.

References

1. Saha, M; et al. Rsk phosphorylation of SOS1 negatively regulates MAPK activation. The Biochemical Journal. 2012, 447 (1): 159-66.
2. Vlahopoulos S; et al. JNK: a key modulator of intracellular signaling. Biochemistry (Mosc). 2004 Aug;69(8):844-54. Review.