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

1  Division of Molecular and Cellular Medicine, Department of Medicine, Albany Medical College and 2  Veterans Affairs Healthcare Network Upstate New York, Albany, New York 12208 Thyroid hormone [ L -thyroxine (T 4 )] rapidly induced phosphorylation and nuclear translocation (activation) of mitogen-...

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Published in:American Journal of Physiology: Cell Physiology 1999-05, Vol.276 (5), p.C1014-C1024
Main Authors: Lin, Hung-Yun, Davis, Faith B, Gordinier, Jennifer K, Martino, Leon J, Davis, Paul J
Format: Article
Language:English
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Summary:1  Division of Molecular and Cellular Medicine, Department of Medicine, Albany Medical College and 2  Veterans Affairs Healthcare Network Upstate New York, Albany, New York 12208 Thyroid hormone [ L -thyroxine (T 4 )] 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 T 4 and agarose-T 4 , 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 STAT1 by T 4 ; they also showed reduced T 4 potentiation of the antiviral action of interferon- (IFN- ). T 4 treatment caused tyrosine-phosphorylated MAPK-STAT1 nuclear complex formation and enhanced Ser-727 phosphorylation of STAT1 , in the presence or absence of IFN- . STAT1 -deficient cells transfected with STAT1 containing an alanine-for-serine substitution at residue 727 (STAT1 A727 ) showed minimal T 4 -stimulated STAT1 activation. IFN- induced the antiviral state in cells containing wild-type STAT1 (STAT1 wt ) or STAT1 A727 ; T 4 potentiated IFN- action in STAT1 wt cells but not in STAT1 A727 cells. T 4 -directed STAT1 Ser-727 phosphorylation is MAPK mediated and results in potentiated STAT1 activation and enhanced IFN- activity. thyroxine; signal transducer and activator of transcription 1 ; signal transduction
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.1999.276.5.c1014