Interaction between mineralocorticoid receptor and epidermal growth factor receptor signaling

The mineralocorticoid receptor (MR) is a steroid receptor that physiologically regulates water and electrolyte homeostasis but that can also induce pathophysiological effects in the renocardiovascular system. Classically, the MR acts as a transcription factor at glucocorticoid response elements but additional protein–protein interactions with other signaling cascades have been described. Of these, the crosstalk with EGFR signaling is especially interesting because various vasoactive substances like angiotensin II and endothelin-1 also mediate their pathophysiological effects via the EGFR. Recently, the MR has been shown to interact nongenomically (via transactivation) and genomically with the epidermal growth factor receptor (via altered expression). These interactions seem to contribute to physiological (e.g. salt homeostasis) as well as pathophysiological (e.g. vascular function) MR effects. The current knowledge on the mechanisms of interaction and on the possible cellular and systemic physiological as well as pathophysiological relevance is reviewed in this article.

► Nuclear mineralocorticoid receptor (MR) stimulates EGFR expression.
► Plasma membrane MR stimulates EGFR transactivation.
► EGFR can integrate MR and angiotensin II action.
► MR–EGFR crosstalk modulates physiological MR actions.
► MR–EGFR crosstalk contributes to pathological MR actions.