serine/threonine protein kinase Sgk1; serum/glucocorticoid-regulated kinase 1 (SGK1, SGK)
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Function
- protein kinase that plays an important role in cellular stress response
- activates certain K+ channels, Na+ channels, & chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability & renal Na+ excretion
- sustained high levels & activity may contribute to conditions such as hypertension & diabetic nephropathy
- mediates cell survival signals, phosphorylates & negatively regulates pro-apoptotic FOXO3A
- phosphorylates NEDD4L, which leads to its inactivation & to the subsequent activation of various channels & transporters such as ENaC, KCNA3/Kv1.3 or EAAT1
- isoform 2 exhibited a greater effect on cell plasma membrane expression of ENaC & Na+ transport than isoform 1
- two specific sites, one in the kinase domain (Thr-256) & the other in the C-terminal regulatory region (Ser-422), need to be phosphorylated for its full activation
- activated by WNK1, WNK2, WNK3 & WNK4 (putative)
- regulated by phosphorylation
- phosphoinositide 3-kinase (PI3-kinase) pathway promotes phosphorylation at Ser-422 which in turn increases the phosphorylation of Thr-256 by PDPK1
- ubiquitinated by NEDD4L; which promotes proteasomal degradation
- ubiquitinated by SYVN1 at the endoplasmic reticulum which promotes rapid proteasomal degradation & maintains a high turnover rate in resting cells
- isoform 2 shows enhanced stability
- isoform 2 resistance to proteasomal degradation is mediated by the sequences within the first 120-amino acid
- interacts with NEDD4 & NEDD4L
Structure
- isoform 2 subcellular localization at the plasma membrane is mediated by the sequences within the first 120 amino acids
- belongs to the protein kinase superfamily, AGC Ser/Thr protein kinase family
- contains 1 AGC-kinase C-terminal domain
- contains 1 protein kinase domain
Compartment
Alternative splicing
Expression
- expressed in most tissues
- expression in the pancreas > placenta, kidney & lung
- isoform 2 is strongly expressed in brain & pancreas > heart, placenta, lung, liver & skeletal muscle
- isoform 1 is induced by serum &/or glucocorticoids
- isoform 2 is not induced by glucocorticoids
- by excessive extracellular glucose & by TGFB1, in cultured cells