Heat shock protein 90 (hsp90) regulates stability and function of many client proteins including members of the NO-cGMP signaling pathway. Soluble guanylate cyclase (sGC), which is the main intracellular receptor of NO, was recently reported to be an hsp90 interacting partner, however, the interaction between the two proteins remains to be characterized and functionally evaluated. In the present study, we show that hsp90 binds to both subunits of the most commonly found sGC isoform, α1β1. Characterization of the region of hsp90 required to bind each subunit in immuno-precipitation experiments, revealed that residues 310-456 of hsp90 interact with both α1 and β1. The region of β1 responsible for binding to hsp90 was mapped in in vitro binding assays and was found to lie between residues 200-408. The importance of the hsp90-sGC interaction was investigated by treating rat smooth muscle cells (RASMC) with the hsp90 inhibitors radicicol (RAD) and geldanamycin (GA) for 1, 24 and 48 hours and determining both sGC activity and protein levels. Long-term (24 or 48 hr) inhibition of hsp90 resulted in a strong decrease of both α1 and β1 protein levels, as well as sGC activity.
|Original language||English (US)|
|Number of pages||3|
|Journal||Review of Clinical Pharmacology and Pharmacokinetics, International Edition|
|State||Published - Mar 19 2004|
ASJC Scopus subject areas
- Pharmacology (medical)