- Poster presentation
- Open Access
Interaction between hsp90 and soluble guanylyl cyclase: physiological significance and mapping of the domains mediating binding
BMC Pharmacology volume 5, Article number: P65 (2005)
Heat shock protein 90 (hsp90) regulates stability and function of many client proteins including members of the NO-cGMP signaling pathway. Soluble guanylyl cyclase (sGC), which is the main intracellular receptor of NO, was recently reported to be an hsp90 interacting partner. In the present study, we show that hsp90 binds to both subunits of the most common sGC form, α1β1. Characterization of the region of hsp90 required to bind each subunit in immunoprecipitation experiments, revealed that residues 310-456 of hsp90 interact with both α1 and β1. The region of β1 responsible for binding to hsp90β was mapped using in vitro binding assays and immunoprecipitation experiments and found to lie in the regulatory domain. The physiological importance of the hsp90/sGC interaction was investigated by treating rat smooth muscle cells (RASMC) with the hsp90 inhibitors radicicol (RAD) and geldanamycin (GA) 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. Moreover, incubation of smooth muscle cells with the proteasome inhibitor MG132 blocked the GA-induced downregulation of sGC. We conclude that the α1 and β1 sGC interact with the M domain of hsp90 and that this interaction regulates the pool of active sGC by affecting the protein levels of the two subunits.
Rights and permissions
Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Zhou, Z., Gerassimou, C., Venema, R.C. et al. Interaction between hsp90 and soluble guanylyl cyclase: physiological significance and mapping of the domains mediating binding. BMC Pharmacol 5 (Suppl 1), P65 (2005). https://doi.org/10.1186/1471-2210-5-S1-P65
- Smooth Muscle Cell
- Proteasome Inhibitor
- Hsp90 Inhibitor
- Client Protein
- Physiological Importance