Increased intracellular calcium activates serum and glucocorticoid-inducible kinase 1 (SGK1) through a calmodulin-calcium calmodulin dependent kinase kinase pathway in Chinese hamster ovary cells.

SGK1 is one of the protein-serine/threonine kinases that is activated by insulin in a PI3K-dependent manner. Although SGK1 mediates a variety of biological activities, the mechanisms regulating its activity remain unclear. In this study, we examined the potential roles of calcium signaling in the activation of SGK1. Treatment of CHO-IR ...
cells with a cell-permeable calcium chelator, BAPTA-AM, abolished the insulin-induced activation of SGK1. Increasing intracellular calcium concentration by treating cells with thapsigargin or ionomycin induced a 6-8 fold increase in SGK1 activation. This was not affected by a PI3K inhibitor, wortmannin, but was completely inhibited by the calmodulin inhibitors, W 7 and W 5. Co-transfection of CHO cells with FLAG-SGK1 and CaMKK revealed the direct association of CaMKK with SGK1. These results suggest a calcium-triggered signaling cascade in which an increase in intracellular calcium concentration directly stimulates SGK1 through CaMKK.
Mesh Terms:
Androstadienes, Animals, CHO Cells, Calcium Signaling, Calcium-Calmodulin-Dependent Protein Kinase Kinase, Calcium-Transporting ATPases, Chelating Agents, Cricetinae, Egtazic Acid, Enzyme Activation, Enzyme Inhibitors, Immediate-Early Proteins, Insulin, Ionomycin, Nuclear Proteins, Plasma Membrane Calcium-Transporting ATPases, Protein-Serine-Threonine Kinases, Sulfonamides, Thapsigargin, Transfection
Life Sci.
Date: Apr. 04, 2003
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