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PTEN and SHIP2 regulates PI3K/Akt pathway through focal adhesion kinase

Amit Gupta1, Chinmoy Sankar Dey

  • 1Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sec. 67, S.A.S. Nagar, Punjab 160 062, India.

Molecular and Cellular Endocrinology
|June 9, 2009
PubMed

Insights

Focal adhesion kinase (FAK) regulates insulin signaling. Insulin resistance causes FAK dephosphorylation via PTEN and SHIP2 phosphatases, impairing glucose uptake in muscle cells.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolic Research

Background:

  • Focal adhesion kinase (FAK) plays a role in insulin signaling.
  • Insulin resistance is linked to decreased FAK tyrosine phosphorylation in skeletal muscle.
  • The precise mechanism of FAK dephosphorylation in insulin resistance is not fully understood.

Purpose of the Study:

  • To investigate the cellular mechanism of FAK dephosphorylation in C2C12 skeletal muscle cells under insulin resistance.
  • To identify the phosphatases responsible for FAK dephosphorylation in this context.

Main Methods:

  • In vitro studies using C2C12 skeletal muscle cells.
  • Analysis of FAK tyrosine phosphorylation levels.
  • Investigation of phosphatase activity, specifically PTEN and SHIP2.

Main Results:

  • Insulin resistance induced dephosphorylation of FAK in C2C12 cells.
  • PTEN and SHIP2 phosphatases were identified as key mediators of FAK dephosphorylation.
  • Upregulation of PTEN and SHIP2 under insulin resistance impairs insulin signaling via FAK.

Conclusions:

  • PTEN and SHIP2 are responsible for FAK dephosphorylation in insulin-resistant skeletal muscle cells.
  • FAK acts as a crucial mediator for PTEN and SHIP2 in regulating insulin signaling.
  • This study elucidates a molecular mechanism underlying insulin resistance in skeletal muscle.

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