Thyroxine promotes association of mitogen-activated protein kinase and nuclear thyroid hormone receptor (TR) and causes serine phosphorylation of TR

Paul J. Davis, Ai Shih, Hung Yun Lin, Leon J. Martino, Faith B. Davis

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

Activated nongenomically by L-thyroxine (T4), mitogen-activated protein kinase (MAPK) complexed in 19-20 min with endogenous nuclear thyroid hormone receptor (TRβ1 or TR) in nuclear fractions of 293T cells, resulting in serine phosphorylation of TR. Treatment of cells with the MAPK kinase inhibitor, PD 98059, prevented both T4-induced nuclear MAPK-TR co-immuno-precipitation and serine phosphorylation of TR. T4 treatment caused dissociation of TR and SMRT (silencing mediator of retinoid and thyroid hormone receptor), an effect also inhibited by PD 98059 and presumptively a result of association of nuclear MAPK with TR. Transfection into CV-1 cells of TR gene constructs in which one or both zinc fingers in the TR DNA-binding domain were replaced with those from the glucocorticoid receptor localized the site of TR phosphorylation by T4-activated MAPK to a serine in the second zinc finger of the TR DNA-binding domain. In an in vitro cell- and hormone-free system, purified activated MAPK phosphorylated recombinant human TRβ1 (102-461). Thus, T4 activates MAPK and causes MAPK-mediated serine phosphorylation of TRβ1 and dissociation of TR and the co-repressor SMRT.

Original languageEnglish
Pages (from-to)38032-38039
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number48
DOIs
Publication statusPublished - Dec 1 2000
Externally publishedYes

Fingerprint

Thyroid Hormone Receptors
Phosphorylation
Cytoplasmic and Nuclear Receptors
Mitogen-Activated Protein Kinases
Thyroxine
Serine
Association reactions
Zinc Fingers
Nuclear Receptor Co-Repressor 2
Zinc
Cell-Free System
HEK293 Cells
DNA
Mitogen-Activated Protein Kinase Kinases
Glucocorticoid Receptors
Retinoids
Transfection

ASJC Scopus subject areas

  • Biochemistry

Cite this

Thyroxine promotes association of mitogen-activated protein kinase and nuclear thyroid hormone receptor (TR) and causes serine phosphorylation of TR. / Davis, Paul J.; Shih, Ai; Lin, Hung Yun; Martino, Leon J.; Davis, Faith B.

In: Journal of Biological Chemistry, Vol. 275, No. 48, 01.12.2000, p. 38032-38039.

Research output: Contribution to journalArticle

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