Related Experiment Video

Updated: Jul 5, 2026

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
11:07

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding

Published on: September 21, 2011

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

Larissa Belova1, Deanna R Brickley, Betty Ky

  • 1Department of Medicine, Committee on Cancer Biology, The University of Chicago, Chicago, Illinois 60637, USA.

The Journal of Biological Chemistry
|May 6, 2008
PubMed

Insights

Heat-shock protein 90 (Hsp90) is essential for serum- and glucocorticoid-regulated kinase-1 (SGK-1) phosphorylation and activity. Hsp90 inactivation disrupts SGK-1 regulation by the phosphoinositide 3-kinase pathway.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Biochemistry

Background:

  • Serum- and glucocorticoid-regulated kinase-1 (SGK-1) is a key regulator of ion channels and epithelial cell proliferation.
  • SGK-1 activity is modulated by transcriptional changes, proteasomal degradation, and phosphorylation.
  • Phosphoinositide 3-kinase (PI3K) signaling is crucial for SGK-1 phosphorylation.

Purpose of the Study:

  • To investigate the role of heat-shock protein 90 (Hsp90) in the regulation of SGK-1 phosphorylation and activity.
  • To elucidate the relationship between Hsp90, PI3K, and SGK-1 signaling.

Main Methods:

  • Utilized geldanamycin to inactivate Hsp90 and LY294002 to inhibit PI3K activity.
  • Assessed SGK-1 phosphorylation levels and kinase activity.
  • Investigated the formation of SGK-1 and Hsp90 complexes.

Main Results:

  • Hsp90 inactivation by geldanamycin decreased SGK-1 phosphorylation independently of proteasomal degradation.
  • PI3K inhibition by LY294002 mimicked the effects of geldanamycin on SGK-1 phosphorylation sites.
  • Geldanamycin identified novel PI3K-dependent phosphorylation sites on SGK-1 beyond known residues.
  • Hsp90 inhibition led to a complete loss of SGK-1 kinase activity.

Conclusions:

  • Hsp90 is essential for PI3K-dependent SGK-1 phosphorylation.
  • Hsp90 plays a critical role in maintaining SGK-1 kinase activity.
  • Hsp90 is a key component in the regulation of the PI3K/SGK-1 signaling pathway.

More Related Videos

Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay06:51

Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay

Published on: July 21, 2021

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...