Thyroid hormone induces activation of mitogen-activated protein kinase in cultured cells

Hung Yun Lin, Faith B. Davis, Jennifer K. Gordinier, Leon J. Martino, Paul J. Davis

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189 Citations (Scopus)


Thyroid hormone [L-thyroxine (T4)] rapidly induced phosphorylation and nuclear translocation (activation) of mitogen-activated protein kinase (MAPK) in HeLa and CV-1 cells in the absence of cytokine or growth factor. A pertussis toxin-sensitive and guanosine 5'-O-(3-thiotriphosphate)-sensitive cell surface mechanism responsive to T4 and agarose-T4, suggesting a G protein-coupled receptor, was implicated. Cells depleted of MAPK or treated with MAPK pathway inhibitors showed reduced activation of MAPK and of the signal transducer and activator of transcription STAT1α by T4; they also showed reduced T4 potentiation of the antiviral action of interferon-γ (IFN-γ). T4 treatment caused tyrosine-phosphorylated MAPK-STAT1α nuclear complex formation and enhanced Ser-727 phosphorylation of STAT1α, in the presence or absence of IFN-γ. STAT1α-deficient cells transfected with STAT1α containing an alanine-for-serine substitution at residue 727 (STAT1α(A727)) showed minimal T4-stimulated STAT1α activation. IFN-γ induced the antiviral state in cells containing wild-type STAT1. (STAT1α(wt)) or STAT1α(A727); T4 potentiated IFN-γ action in STAT1α(wt) cells but not in STAT1α(A727) cells. T4-directed STAT1α Ser-727 phosphorylation is MAPK mediated and results in potentiated STAT1α activation and enhanced IFN-γ activity.

Original languageEnglish
Pages (from-to)C1014-C1024
JournalAmerican Journal of Physiology - Cell Physiology
Issue number5 45-5
Publication statusPublished - 1999
Externally publishedYes


  • Signal transducer and activator of transcription 1α
  • Signal transduction
  • Thyroxine

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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