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Am J Physiol Heart Circ Physiol 295: H361-H365, 2008. First published May 9, 2008; doi:10.1152/ajpheart.00825.2007
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Proteins interact with the cytosolic mineralocorticoid receptor depending on the ligand

Miriam Weber, Martin Wehling, and Ralf Lösel

Clinical Pharmacology Mannheim, Department of Experimental and Clinical Pharmacology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Submitted 16 July 2007 ; accepted in final form 6 May 2008

Steroid receptors belonging to the superfamily of nuclear receptors do not exist as single monomeric proteins but mediate their effects by the interaction with numerous other proteins, e.g., cofactors for transcription, but also other proteins involved in cellular signaling. This interaction may be ligand dependent, which explains the differential effects of receptor ligands. Whereas some receptors, e.g., the estrogen receptor, have been studied in great detail, much less is known about proteins interacting with the mineralocorticoid receptor (MR). In this study, we aimed to identify interacting proteins using a proteomics approach involving tagged receptor constructs. After affinity isolation of MR complexes, blue native electrophoresis revealed the presence of several populations of MR complexes differing in size and composition. During the identification of interacting proteins, various heat shock proteins but also several previously undescribed potential interactors were found, including 14-3-3-{varepsilon}. We also demonstrate here that the cytosolic MR in the presence of detergent interacts in a ligand-selective manner with glucose-regulated protein 78 and propionyl-CoA carboxylase-β precursor, which are found in the unliganded or aldosterone-containing complex but not with spironolactone.

steroid receptor; aldosterone; mineralocorticoid; spironolactone; 14-3-3; proteomics



Address for reprint requests and other correspondence: M. Wehling, Klinische Pharmakologie Mannheim, Klinikum Mannheim, Theodor-Kutzer-Ufer, 68167 Mannheim, Germany (e-mail: martin.wehling{at}pharmtox.uni-heidelberg.de)







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