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SHP-2 regulates myogenesis by coupling to FAK signaling pathway

Michel V de Oliveira1, Talita M Marin, Carolina F Clemente

  • 1Department of Internal Medicine, School of Medicine State University of Campinas, Brazil.

FEBS Letters
|August 25, 2009
PubMed

Insights

Focal adhesion kinase (FAK) dephosphorylation, mediated by SHP-2, is crucial for initiating muscle cell differentiation (myogenesis) by controlling cell cycle withdrawal.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Transient dephosphorylation of Focal Adhesion Kinase (FAK) at Tyr-397 is essential for early cell cycle withdrawal during myogenesis.
  • The precise molecular mechanisms regulating FAK activity during muscle differentiation remain incompletely understood.

Purpose of the Study:

  • To elucidate the role of SH2-containing protein tyrosine phosphatase 2 (SHP-2) in FAK dephosphorylation during myogenesis.
  • To investigate the mechanistic link between SHP-2, FAK, and the initiation of C2C12 myoblast differentiation.

Main Methods:

  • Utilized C2C12 myoblasts subjected to serum starvation to induce differentiation.
  • Employed RNA interference (RNAi) to knockdown SHP-2 expression.
  • Assessed FAK dephosphorylation, SHP-2 activation and association with FAK, cell cycle status, and differentiation into myotubes.

Main Results:

  • Serum starvation of C2C12 myoblasts induced transient FAK dephosphorylation, coinciding with SHP-2 activation and its association with FAK.
  • SHP-2 knockdown via RNAi inhibited the upregulation of SHP-2 and the dephosphorylation of FAK during myogenesis.
  • Depletion of SHP-2 significantly delayed cell cycle withdrawal and the differentiation of myoblasts into myotubes.

Conclusions:

  • SHP-2 plays a critical role in the dephosphorylation of FAK during myogenesis.
  • The FAK/SHP-2 complex is essential for triggering myogenesis by facilitating cell cycle withdrawal and differentiation.
  • These findings provide a mechanistic explanation for reduced FAK activity during muscle differentiation.

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