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Involvement of the protein kinase C pathway in thyrotropin-induced STAT3 activation in FRTL-5 thyroid cells

Y J Park1, E S Park, M S Kim

  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, 28 Yongon-dong Chongno-gu, 110-744 Seoul, South Korea.

Molecular and Cellular Endocrinology
|September 21, 2002
PubMed

Insights

Thyrotropin (TSH) activates STAT3 through the TSH receptor. This study reveals that both cyclic AMP (cAMP) and protein kinase C (PKC) pathways are involved in TSH-induced STAT3 activation.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Signaling

Background:

  • Thyrotropin (TSH) binding to its receptor (TSHR) activates cAMP-protein kinase A (PKA) and protein kinase C (PKC) pathways.
  • TSH also activates the Janus kinases (JAK)/signal transducer and activator of transcription (STAT) pathway via TSHR.

Purpose of the Study:

  • To investigate the involvement of cAMP/PKA or PKC systems in STAT3 activation by TSH.
  • To elucidate the signaling mechanisms downstream of TSHR activation.

Main Methods:

  • TSH treatment of FRTL-5 thyrocytes and human TSHR-expressing CHO cells.
  • Inhibition studies using a blocking antibody against TSHR, PKA inhibitors, and PKC inhibitors.
  • Assessment of STAT3 phosphorylation as a marker of activation.

Main Results:

  • TSH treatment led to STAT3 phosphorylation in both cell types.
  • TSH-induced STAT3 activation was blocked by a TSHR antibody.
  • Increased intracellular cAMP activated STAT3, but PKA inhibition did not affect it.
  • PKC activation (PMA) induced STAT3 phosphorylation, and PKC inhibitors blocked this.
  • PKC inhibition also blocked STAT3 activation induced by cAMP stimulation.

Conclusions:

  • TSH activates STAT3 via TSHR through both cAMP- and PKC-dependent pathways.
  • Protein kinase C (PKC) appears to be involved in the signaling pathway downstream of cAMP in response to TSH.

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