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ERK5/MAPK is activated by TGFbeta in hepatocytes and required for the GSK-3beta-mediated Snail protein stabilization

Alessandra Marchetti1, Marta Colletti, Angela Maria Cozzolino

  • 1Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, Rome, Italy. marchetti@bce.uniroma1.it

Cellular Signalling
|September 2, 2008
PubMed

Insights

Extracellular signal-regulated protein kinase 5 (ERK5) is activated by TGFbeta in liver cells, influencing cell growth and survival. This study reveals ERK5

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Hepatology

Background:

  • Extracellular signal-regulated protein kinase 5 (ERK5) is a key regulator of cellular processes like proliferation, survival, differentiation, and apoptosis.
  • The MEK5/ERK5 module is integral to various signal transduction pathways.
  • Transforming growth factor-beta (TGFbeta) is a multifunctional cytokine crucial for regulating hepatic growth.

Purpose of the Study:

  • To investigate the role of ERK5 in TGFbeta signaling within hepatocytes.
  • To elucidate the mechanisms by which ERK5 influences TGFbeta-mediated cellular responses.

Main Methods:

  • Investigated ERK5 activation kinetics in hepatocytes stimulated with TGFbeta.
  • Utilized Src-dependent pathway analysis.
  • Examined the impact of ERK5 on Snail protein regulation and glycogen synthase kinase-3beta (GSK3beta) inactivation.

Main Results:

  • TGFbeta rapidly and sustainably phosphorylates and activates ERK5 in hepatocytes via a Src-dependent pathway.
  • ERK5 is essential for the stabilization of Snail protein induced by TGFbeta.
  • ERK5 inactivation prevents TGFbeta-mediated GSK3beta inactivation, a mechanism linked to Snail stabilization.

Conclusions:

  • This study establishes a novel role for ERK5 in TGFbeta signaling in hepatocytes.
  • ERK5 mediates TGFbeta-induced Snail protein stabilization through GSK3beta inactivation.
  • Uncovered a new mechanism linking ERK5 to TGFbeta-induced cellular responses in the liver.

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