Phosphorylation: a fundamental regulator of steroid receptor action

• Multiple kinases phosphorylate steroid hormone receptors and their coregulators.
• Site-specific phosphorylation modulates the selective actions of receptors.
• Activation of cell signaling pathways impacts upon the biological response of receptors.
• Regulation of receptor function by cell signaling is relevant to human disease.

Steroid hormone receptors (SHRs) are hormone-activated transcription factors involved in numerous cellular functions and in health and disease. Their activities depend on the cellular level of the receptor, the presence of coregulator proteins, and the cell signaling pathways that are active in the cell. SHRs and their coregulators are phosphorylated on multiple sites by a wide variety of kinases. Each site may contribute to multiple functions and the net effect of an individual phosphorylation depends on the activating kinase. Here we discuss functions of known SHR phosphorylation sites, kinase regulation, evidence of translational relevance, and crosstalk between SHRs and cell signaling pathways. Understanding how cell signaling pathways regulate SHRs might yield novel therapeutic targets for multiple human diseases.