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Updated: May 16, 2026

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Published on: January 27, 2012

FAK regulates Cdk2 in EGF-stimulated primary cultures of hepatocytes

Liv Ingrid Flinder1, Lene Wierød, Carola M Rosseland

  • 1Laboratory for Toxicopathology, Institute of Pathology, Oslo University Hospital, University of Oslo, Oslo, Norway.

Journal of Cellular Physiology
|November 22, 2012
PubMed

Insights

Focal adhesion kinase (FAK) regulates cell cycle entry by controlling Cdk2 levels in hepatocytes. This finding reveals FAK

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cellular processes like proliferation and motility depend on anchorage-dependent signaling.
  • Focal adhesion kinase (FAK) plays a role in cell signaling pathways.
  • Cyclin-dependent kinase 2 (Cdk2) is crucial for cell cycle progression.

Purpose of the Study:

  • To investigate the novel role of FAK in regulating Cdk2 in primary cultured hepatocytes.
  • To elucidate the mechanism by which FAK mediates Cdk2 regulation in response to growth factors.

Main Methods:

  • Utilized FAK inhibition and specific FAK mutants (FAKY397F, FAKY925F, FAKY861F) in primary cultured hepatocytes.
  • Assessed S-phase entry, protein expression, and nuclear accumulation of cell cycle regulators (Cdk2, cyclin E, p27, cyclin D1).
  • Investigated the impact of FAK on epidermal growth factor (EGF) and hepatocyte growth factor (HGF) signaling, including cell spreading and survival.

Main Results:

  • FAK inhibition reduced S-phase entry, Cdk2 expression, and nuclear accumulation in response to EGF.
  • FAK regulates Cdk2 levels, influencing the expression of its inhibitor p27.
  • Specific FAK phosphorylation sites are critical for EGF-induced ERK activity and Cdk2 expression, and FAK is essential for HGF-mediated proliferation and growth factor-induced cell spreading.

Conclusions:

  • FAK acts as a central coordinator of integrin and growth factor signaling for S-phase entry.
  • FAK regulates Cdk2, a key G1/S-phase transition regulator.
  • Integrins and growth factors cooperate through FAK in anchorage-dependent signaling pathways that control proliferation and motility.

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