Hsp90 regulates the phosphorylation and activity of serum- and glucocorticoid-regulated kinase-1

Larissa Belova, Deanna R. Brickley, Betty Ky, Sanjay K. Sharma, Suzanne D. Conzen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

SGK-1 (serum- and glucocorticoid-regulated kinase-1), a member of the AGC protein kinase family, plays an important role in regulating ion channel expression and contributes to malignant epithelial cell proliferation and survival. SGK-1 activity is regulated on three levels: transcriptional induction following a variety of environmental and intracellular stresses, proteasomal degradation, and phosphorylation. Here we report that phosphoinositide 3-kinase (PI3K)-dependent phosphorylation of SGK-1 requires formation of a complex between SGK-1 and heat-shock protein 90 (Hsp90). Inactivation of Hsp90 by geldanamycin led to decreased SGK-1 phosphorylation independently of increased proteasomal protein degradation, and inhibition of PI3K activity by LY294002 appeared to eliminate SGK-1 phosphorylation at the same residues as those affected by geldanamycin treatment. Interestingly, geldanamycin-targeted phosphorylation sites were not limited to the known conserved PI3K-dependent sites Thr-256 and Ser-422 in SGK-1 but included additional unknown PI3K-dependent residues. Inhibition of Hsp90 also resulted in a complete loss of SGK-1 kinase activity, suggesting that Hsp90 activity is essential for regulating the PI3K/SGK-1 pathway.

Original languageEnglish (US)
Pages (from-to)18821-18831
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number27
DOIs
StatePublished - Jul 4 2008
Externally publishedYes

Fingerprint

HSP90 Heat-Shock Proteins
Phosphorylation
1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
Phosphotransferases
serum-glucocorticoid regulated kinase
Degradation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Cell proliferation
Ion Channels
Protein Kinases
Proteolysis
Cell Survival
Epithelial Cells
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hsp90 regulates the phosphorylation and activity of serum- and glucocorticoid-regulated kinase-1. / Belova, Larissa; Brickley, Deanna R.; Ky, Betty; Sharma, Sanjay K.; Conzen, Suzanne D.

In: Journal of Biological Chemistry, Vol. 283, No. 27, 04.07.2008, p. 18821-18831.

Research output: Contribution to journalArticle

Belova, Larissa ; Brickley, Deanna R. ; Ky, Betty ; Sharma, Sanjay K. ; Conzen, Suzanne D. / Hsp90 regulates the phosphorylation and activity of serum- and glucocorticoid-regulated kinase-1. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 27. pp. 18821-18831.
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