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Rsk2 allosterically activates estrogen receptor α by docking to the hormone-binding domain

By David E. Clark, Celeste E. Poteet-Smith, Jeffrey A. Smith and Deborah A. Lannigan

Abstract

We describe a novel mechanism for transcriptional regulation, in which docking of p90 ribosomal S6 kinase 2 (Rsk2) to the hormone-binding domain (HBD) of estrogen receptor α (ERα) induces a conformational change that enhances the transcriptional activation function contained in the HBD. A constitutively active mutant of Rsk2 specifically enhances ERα-mediated transcription by phosphorylation of Ser167 in ERα and by physically associating with residues 326–394 of the ERα HBD. The anti-estrogen 4-hydroxytamoxifen blocks Rsk2-mediated activation of ERα, by inducing a conformation of ERα in which the Rsk2 docking site is masked. Transcriptional activation and docking are specific for ERα and do not occur with the related isoform, ERβ. ERα phosphorylation, docking and transcriptional activation are regulated by the Rsk2 N-terminal kinase domain. The allosteric regulation of a target protein, independent of phosphorylation, may be paradigmatic of a general function for protein kinase docking sites

Topics: Article
Publisher: Oxford University Press
Year: 2001
DOI identifier: 10.1093/emboj/20.13.3484
OAI identifier: oai:pubmedcentral.nih.gov:125527
Provided by: PubMed Central
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