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
Abstract
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.
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Activation of SGK1 can increase cytoplasmic calcium levels, thereby compromising integrity of BBB.
“activation of SGK1, which can increase cytoplasmic calcium levels, thereby compromising the integrity of the BBB”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Imai et al., 2003
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- Authors
- Imai, S., Okayama, N., Shimizu, M., & Itoh, M.
- Affiliations
- Nagoya City University (JP)
- ORCID
- Itoh, Makoto
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2003-04
- Volume
- 72
- Issue
- 20
- Pages
- 2199-2209
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2030181672
- Cited by
- 32
- References
- 27
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 9 · 2023: 1 · 2022: 1 · 2021: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2013: 2
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- SGK1, serum- and glucocorticoid-inducible kinase 1, intracellular calcium, calcium signaling, CaMKK, calmodulin, insulin signaling, thapsigargin, ionomycin, BAPTA-AM, calmodulin antagonists, protein kinase activation, CHO cells
- MeSH terms
- Wortmannin, Serum-Glucocorticoid Regulated Kinases, Calcium-Transporting ATPases, Androstadienes, Animals, Chelating Agents, Egtazic Acid, Enzyme Activation, Enzyme Inhibitors, Cricetinae, Insulin, Nuclear Proteins, Sulfonamides, Transfection, Ionomycin, CHO Cells, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Thapsigargin, Calcium Signaling, Plasma Membrane Calcium-Transporting ATPases, Calcium-Calmodulin-Dependent Protein Kinase Kinase
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