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Posttranslational Modification of Thyroid Hormone Nuclear Receptor by Phosphorylation

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1801)

Abstract

TR phosphorylation promotes TR binding to DNA and heterodimerization with RXR. TRβ phosphorylation is induced by thyroid hormone on the cell membrane and phosphorylation by extracellular signal-regulated kinases (ERK), presumably at serine 142. TRα1 N-termini harbors two phosphorylation sites at serine 12 and serine 28/29. Serine 12 is phosphorylated by casein 2 and serine 28/29 by protein kinase A. Mutation analysis of TRα2 identified 2 serine sites, S472 and S473, as the substrates for casein kinase II. Phosphorylated TRα2 does not bind to DNA and dephosphorylated TRα binds to DNA and antagonizes TRα1 binding. Phosphorylation of TR is critical for TR function and T3 signaling and approaches to detection and analysis of phosphorylated TR are described.

Key words

Thyroid hormone receptor (TR) In vivo (cells) phosphorylation In vivo (tissue) phosphorylation 

Notes

Acknowledgments

This work was supported by NIH grant RO1DK98576 and VA Merit Review funds.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of MedicineDavid Geffen School of Medicine at UCLA and VA Greater Los Angles Healthcare SystemLos AngelesUSA
  2. 2.Department of PhysiologyDavid Geffen School of Medicine at UCLA and VA Greater Los Angles Healthcare SystemLos AngelesUSA

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