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 journalArticlepeer-review

13 Scopus citations


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
Issue number27
StatePublished - Jul 4 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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