Disparate effects of thyroid hormone on actions of epidermal growth factor and transforming growth factor-α are mediated by 3′,5′-cyclic adenosine 5′-monophosphate-dependent protein kinase II

Ai Shih, Shenli Zhang, H. James Cao, Heng Yuan Tang, Faith B. Davis, Paul J. Davis, Hung Yun Lin

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Epidermal growth factor (EGF) and TGFα share the same plasma membrane receptor. In the present studies in HeLa cells, both EGF and TGFα caused MAPK (ERK1/2) activation and expression of the immediate-early gene c-fos. Thyroid hormone (T 4) nongenomically enhanced EGF- and TGFα-induced MAPK activation. This T 4 action was duplicated by T 4-agarose and blocked by tetraiodothyroacetic acid, which inhibits binding of T 4 to plasma membranes. TGFα-induced MAPK activation was potentiated by 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP) but not 8-chloro-cyclic adenosine monophosphate. TGFα, T 4, and 8-Br-cAMP each caused protein kinase A (PKA) II serine phosphorylation, whereas phosphorylation of PKA-II was not seen in cells treated with EGF or 8-chloro-cyclic adenosine monophosphate. In a PKA activity assay, the enzyme was stimulated by T 4, EGF, and TGFα; T 4 enhanced the effect of TGFα but not that of EGF. T 4, although it potentiated c-fos gene expression in EGF-treated cells, suppressed this effect in cells treated with TGFα. Cells exposed to 8-Br-cAMP also inhibited TGFα-stimulated c-fos expression. Studies of cell proliferation indicated that T 4 potentiated EGF action but inhibited that effect in TGFα-treated cells. The disparate effects of T 4 on actions of EGF and TGFα, which share the same cell surface receptor, are mediated by hormone phosphorylation and activation of PKA-II.

Original languageEnglish
Pages (from-to)1708-1717
Number of pages10
JournalEndocrinology
Volume145
Issue number4
DOIs
Publication statusPublished - Apr 2004
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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