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Acta Physiologica 2009; Volume 195, Supplement 669
The 88th Annual Meeting of The German Physiological Society
3/22/2009-3/25/2009
Giessen, Germany
DIRECT INTERACTION OF MINERALOCORTICOID RECEPTOR AND EGF RECEPTOR
Abstract number: O514
Grossmann1 C., Husse1 B., Mildenberger1 S., Schreier1 B., Gekle1 M.
1Julius-Bernstein-Institut fr Physiologie, Halle/Saale
The mineralocorticoid receptor (MR) regulates salt homeostasis and mediates pathophysiological remodelling processes in various tissues, like heart, vessels and the kidney. Pathophysiological relevant signaling mechanisms include classical genomic but also nongenomic pathways, involving transactivation of the epidermal growth factor receptor (EGFR). We investigated the MR-EGFR interaction by coimmunoprecipitation, confocal microscopy and fluorescence resonance energy transfer (FRET) using tagged MR and anti-EGFR antibodies. EGFR and a small fraction of MR colocalize and interact at or in the vicinity of the cell membrane, independent of receptor ligands. However, MR transactivates EGFR only when stimulated. Experiments with deletion constructs reveal that the interaction is accomplished by the c-terminal EF domains of MR. Release of MR from the HSP90 complex by geldanamycin enhances the MR fraction interacting with EGFR and MR-EGFR signaling. Our data suggest that a small fraction of MR forms a signaling complex with or close to the EGFR independent of HSP90.
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Acta Physiologica 2009; Volume 195, Supplement 669 :O514