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

研究成果: 雜誌貢獻文章

184 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)38032-38039
頁數8
期刊Journal of Biological Chemistry
275
發行號48
DOIs
出版狀態已發佈 - 十二月 1 2000
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry

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