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The RXR heterodimers and orphan receptors.

D. Mangelsdorf,R. Evans

Published 1995 in Cell

ABSTRACT

The nuclear receptor superfamily is comprised of over 150 different proteins that have evolved to mediate a complex array of extracellular signals into transcriptional responses. Many, but not all, of these proteins directly bind to signaling molecules, which, because of their small lipophilic character, can easily enter the target cell. Thus, unlike membrane-bound receptors, the nuclear receptors are intracellular and function to control the activity of target genes directly. In aggregate, these target genes comprise a genetic network whose coordinate activity defines the physiologic response. The purpose of this review is to establish the historical links between the steroid and nonsteroid receptor signaling systems, to chart the explosive development of the retinoid X receptor (RXR) heterodimer and orphan receptor family, to explain the impact of these discoveries on our understanding of the mechanisms of hormonal signaling, and, finally, to present emerging issues and implications of these studies for animal development, physiology, and human disease.

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