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Protein kinase C modulates negatively the hepatocyte growth factor-induced migration, integrin expression and

Annamária Gujdár1, Szabolcs Sipeki, Erzsébet Bander

  • 1Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, P.O. Box 260, 1444, Budapest, Hungary.

Cellular Signalling
|January 8, 2004
PubMed

Insights

Protein kinase C (PKC) negatively regulates hepatocyte growth factor (HGF)-induced integrin expression by limiting Erk1/Erk2 and phosphatidylinositol 3-kinase (PI 3K) activation. Inhibiting PKC enhances integrin expression and prolongs MAP kinase activation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein kinase C (PKC) was previously shown to decrease the duration of Erk1/Erk2 MAP kinase activation in hepatocyte growth factor (HGF)-induced HepG2 cells.
  • Integrin expression plays a crucial role in cell adhesion and migration, processes often dysregulated in disease.

Purpose of the Study:

  • To investigate the role of PKC in regulating HGF-induced integrin expression.
  • To elucidate the signaling pathways, including Erk1/Erk2 and phosphatidylinositol 3-kinase (PI 3K), involved in HGF-induced integrin expression.

Main Methods:

  • Utilized HepG2 cells stimulated with HGF and epidermal growth factor (EGF).
  • Assessed integrin expression levels.
  • Measured the activation of Erk1/Erk2 MAP kinase and PI 3K.
  • Employed PKC inhibition as a key experimental manipulation.

Main Results:

  • Inhibition of PKC significantly enhanced HGF-induced integrin expression.
  • Prolonged activation of Erk1/Erk2 was observed alongside enhanced integrin expression.
  • PI 3K activity was essential for growth factor-induced integrin expression.
  • PKC inhibition prevented the decrease in PI 3K activation following HGF stimulation, unlike in EGF-stimulated cells.

Conclusions:

  • PKC acts as a negative modulator of HGF-induced integrin expression.
  • The findings highlight a crosstalk between PKC, Erk1/Erk2, and PI 3K signaling in regulating integrin expression.
  • PKC's modulation of these pathways influences the HGF-induced mitogenic response.

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