Posttranslational Modification of Thyroid Hormone Nuclear Receptor by Phosphorylation
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 wordsThyroid hormone receptor (TR) In vivo (cells) phosphorylation In vivo (tissue) phosphorylation
This work was supported by NIH grant RO1DK98576 and VA Merit Review funds.
- 5.Goldberg Y, Glineur C, Gesquiere JC, Ricouart A, Sap J, Vennstrom B, Ghysdael J (1988) Activation of protein kinase C or cAMP-dependent protein kinase increases phosphorylation of the c-erbA-encoded thyroid hormone receptor and of the v-erbA-encoded protein. EMBO J 7:2425–2433PubMedPubMedCentralCrossRefGoogle Scholar