SGK1 is a protein kinase that plays an important role in cellular stress response. SGK1 activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. Sustained high levels of SGK1 and activity may contribute to conditions such as hypertension and diabetic nephropathy. This protein also mediates cell survival signals, as it has been shown to phosphorylate and negatively regulate the pro apoptotic FOXO3A protein. Ser 422 is a critical site on the protein and may be involved in its activation.
Expressed in most tissues with highest levels in the pancreas, followed by placenta, kidney and lung. Isoform 2 is strongly expressed in brain and pancreas, weaker in heart, placenta, lung, liver and skeletal muscle.
翻译后修饰
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 and 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.
相似性
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. Contains 1 AGC-kinase C-terminal domain. Contains 1 protein kinase domain.
功能
Protein kinase that plays an important role in cellular stress response. Activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability and renal sodium excretion. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Mediates cell survival signals, phosphorylates and negatively regulates pro-apoptotic FOXO3A. Phosphorylates NEDD4L, which leads to its inactivation and to the subsequent activation of various channels and transporters such as ENaC, KCNA3/Kv1.3 or EAAT1. Isoform 2 exhibited a greater effect on cell plasma membrane expression of ENaC and Na(+) transport than isoform 1.