Human steroid receptors and erb-A gene products form a superfamily of enhancer-binding proteins.

Steroid hormones exert potent effects on development and differentiation, and their actions are mediated as a consequence of their interaction with specific, high-affinity binding proteins referred to as receptors. To initiate the analysis of the molecular mechanisms by which steroid receptor molecules regulate transcription, we have recently cloned the human glucocorticoid receptor cDNA. The structural analysis of receptor clones reveals 2 protein forms termed 'alpha' and 'beta' which differentiate their carboxy termini. The alpha-receptor is equivalent to the major form of the human glucocorticoid receptor and appears to be the molecule that confers transcriptional control. This protein contains a cysteine-rich region which we believe defines the DNA-binding domain. Structural analysis reveals the receptor to be related to a novel family of proto-oncogenes termed 'erb-A'. To examine this relationship, we have cloned certain members of the erb proto-oncogene family which reveals strong relatedness to the DNA-binding domain of the glucocorticoid receptor. Based on these homologies, we proposed that erb-A protooncogenes are transacting factors that may be candidates for enhancer sequence binding proteins. The unexpected indication from this study is that the steroid receptors and the erb-A proto-oncogenes share a common primordial archetype and therefore appear to be members of new super family of regulatory proteins.