We have examined the effects of l-thyroxine (T4) on the activation of signal transducer and activator of transcription 3 (STAT3) and on the STAT3-dependent induction of c-Fos expression by epidermal growth factor (EGF). T4, at a physiological concentration of 100 nM, caused tyrosine phosphorylation and nuclear translocation (i.e. activation) of STAT3 in HeLa cells in as little as 10–20 min. Activation by T4 of STAT3 was maximal at 30 min (15±4-fold enhancement; mean±S.E.M.) in 18 experiments. This effect was reproduced by T4–agarose (100 nM) and blocked by CGP 41251, genistein, PD 98059 and geldanamycin, inhibitors of protein kinase C (PKC), protein tyrosine kinase (PTK), mitogen-activated protein kinase (MAPK) kinase and Raf-1 respectively. Tyrosine-phosphorylated MAPK also appeared in nuclear fractions within 10 min of treatment with T4. In the nuclear fraction of T4-treated cells, MAPK immunoprecipitate also contained STAT3. The actions of T4 were similar in HeLa and CV-1 cells, which lack thyroid hormone receptor (TR), and in TR-replete skin fibroblasts (BG-9). T4 also potentiated the EGF-induced nuclear translocation of activated STAT1α and STAT3 and enhanced the EGF-stimulated expression of c-Fos. Hormone potentiation of EGF-induced signal transduction and c-Fos expression was inhibited by CGP 41251, geldanamycin and PD 98059. Therefore the non-genomically induced activation by T4 of STAT3, and the potentiation of EGF by T4, require activities of PKC, PTK and an intact MAPK pathway.
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March 1999
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Research Article|
February 22 1999
Thyroid hormone promotes the phosphorylation of STAT3 and potentiates the action of epidermal growth factor in cultured cells
Hung-Yun LIN
;
Hung-Yun LIN
1
*Molecular and Cellular Medicine Program, Department of Medicine, Albany Medical College, Albany, NY 12208, U.S.A.
†Veterans Affairs Healthcare Network Upstate New York at Albany, Albany, NY 12208, U.S.A.
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Ai SHIH
;
Ai SHIH
1
*Molecular and Cellular Medicine Program, Department of Medicine, Albany Medical College, Albany, NY 12208, U.S.A.
†Veterans Affairs Healthcare Network Upstate New York at Albany, Albany, NY 12208, U.S.A.
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Faith B. DAVIS
;
Faith B. DAVIS
*Molecular and Cellular Medicine Program, Department of Medicine, Albany Medical College, Albany, NY 12208, U.S.A.
†Veterans Affairs Healthcare Network Upstate New York at Albany, Albany, NY 12208, U.S.A.
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Paul J. DAVIS
Paul J. DAVIS
2
*Molecular and Cellular Medicine Program, Department of Medicine, Albany Medical College, Albany, NY 12208, U.S.A.
†Veterans Affairs Healthcare Network Upstate New York at Albany, Albany, NY 12208, U.S.A.
2To whom correspondence should be addressed at the Department of Medicine, Albany Medical College (e-mail pjdavis@albany.net).
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Biochem J (1999) 338 (2): 427–432.
Article history
Received:
July 09 1998
Revision Received:
November 11 1998
Accepted:
December 07 1998
Citation
Hung-Yun LIN, Ai SHIH, Faith B. DAVIS, Paul J. DAVIS; Thyroid hormone promotes the phosphorylation of STAT3 and potentiates the action of epidermal growth factor in cultured cells. Biochem J 1 March 1999; 338 (2): 427–432. doi: https://doi.org/10.1042/bj3380427
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