Thyroid hormone promotes the phosphorylation of STAT3 and potentiates the action of epidermal growth factor in cultured cells

Abstract

We have examined the effects of -thyroxine (T % ) 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). T % , 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 T % of STAT3 was maximal at 30 min (15p4-fold enhancement ; meanpS.E.M.) in 18 experiments. This effect was reproduced by T % -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 T % .

Integrin αVβ3 Contains a Cell Surface Receptor Site for Thyroid Hormone that Is Linked to Activation of Mitogen-Activated Protein Kinase and Induction of Angiogenesis

“…Our laboratory has shown in the CV-1 monkey fibroblast cell line, which lacks functional TR, and in other cells that T 4 activates the MAPK (ERK1/2) signaling cascade and promotes the phosphorylation and nuclear translocation of MAPK as early as 10 min after application of a physiological concentration of T 4 (6,19). In nuclear fractions of thyroid hormone-treated cells, we have described complexes of activated MAPK and transactivator nucleoproteins that are substrates for the serine kinase activity of MAPK.…”

Thyroid Hormone Promotes Serine Phosphorylation of p53 by Mitogen-Activated Protein Kinase

“…The primary nuclear localization signal for p53 is in the region of serine 316 (11). A role for mitogen-activated protein kinase (MAPK) 1 in the serine phosphorylation of p53 has been described (12), but the mechanism for regulation of this action of MAPK is not known.We have recently shown in several cell lines that thyroid hormone nongenomically promotes phosphorylation and nuclear uptake of MAPK (13,14). Activated by a physiologic concentration of L-thyroxine (T 4 ), nuclear MAPK is able to complex with and serine phosphorylate signal transducer and activator of transcription (STAT) proteins STAT1R (13) and STAT3 (14), enhancing their transcriptional activities.…”

l-Triiodothyronine differentially and nongenomically regulates synaptosomal protein phosphorylation in adult rat brain cerebral cortex: Role of calcium and calmodulin

“…Decreased levels of phosphorylated MAPK were noticed in hippocampus from intact adult hypothyroid rat brain (Gerges and Alkadhi, 2004). In 293T cells, THs nongenomically promoted MAPK-mediated phosphorylation of nuclear TH receptor α-1 isoform (Lin et al, 1999;Shih et al, 2001). TH-induced MAPK phosphorylation in a variety of intact cell lines was shown to be mediated via a G-protein (Lin et al, 2003;Tang et al, 2004).…”