Catalytic activity:ATP + a protein = ADP + a phosphoprotein. ,enzyme regulation:Two specific sites , one in the kinase domain (Thr-256) and the other in the C-terminal regulatory region (Ser-422) , need to be phosphorylated for its full activation. ,Function: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 , Kv1.3 , or EAAT1. ,induction:By serum and/or glucocorticoids. By excessive extracellular glucose and by TGF-beta , in cultured cells. ,PTM: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. ,PTM: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. ,similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. ,similarity:Contains 1 AGC-kinase C-terminal domain. ,similarity:Contains 1 protein kinase domain. ,subcellular location:Nuclear , upon phosphorylation. ,subunit:Interacts with NEDD4 and NEDD4L. ,tissue specificity:Expressed in most tissues with highest levels in the pancreas , followed by placenta , kidney and lung. ,
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