Abstract
SGK-1 (serum- and glucocorticoid-regulated kinase-1) is a stress-induced serine/threonine kinase that is phosphorylated and activated downstream of PI3K (phosphoinositide 3-kinase). SGK-1 plays a critical role in insulin signalling, cation transport and cell survival. SGK-1 mRNA expression is transiently induced following cellular stress, and SGK-1 protein levels are tightly regulated by rapid proteasomal degradation. In the present study we report that SGK-1 forms a complex with the stress-associated E3 ligase CHIP [C-terminus of Hsc (heat-shock cognate protein) 70-interacting protein]; CHIP is required for both the ubiquitin modification and rapid proteasomal degradation of SGK-1. We also show that CHIP co-localizes with SGK-1 at or near the endoplasmic reticulum. CHIP-mediated regulation of SGK-1 steady-state levels alters SGK-1 kinase activity. These data suggest a model that integrates CHIP function with regulation of the PI3K/ SGK-1 pathway in the stress response.
Original language | English (US) |
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Pages (from-to) | 235-244 |
Number of pages | 10 |
Journal | Biochemical Journal |
Volume | 400 |
Issue number | 2 |
DOIs | |
State | Published - Dec 1 2006 |
Externally published | Yes |
Keywords
- C-terminus of Hsc70 interacting protein (CHIP) E3 ligase
- Cell survival
- Phosphoinositide 3-kinase (PI3K)
- Serum and glucocorticoid-regulated kinase-1 (SGK-1)
- Stress response
- Ubiquitination
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology