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Tac-beta1 inhibits FAK activation and Src signaling

Allison L Berrier1, Christopher W Jones, Susan E LaFlamme

  • 1Center for Cell Biology and Cancer Research, Albany Medical Center, 47 New Scotland Avenue, Albany, NY 12208, USA.

Biochemical and Biophysical Research Communications
|January 17, 2008
PubMed

Insights

The chimeric Tac-beta1 receptor blocks cell spreading by inhibiting focal adhesion kinase (FAK) activation. This prevents downstream signaling, including Src activation, crucial for cell adhesion and spreading.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Integrin signaling pathways

Background:

  • Integrin binding to the extracellular matrix initiates signals promoting cell spreading.
  • Previous studies showed that the chimeric Tac-beta1 receptor inhibits cell spreading.

Purpose of the Study:

  • To elucidate the mechanism by which Tac-beta1 inhibits cell spreading.
  • To investigate the effect of Tac-beta1 on early signaling events, specifically focal adhesion kinase (FAK) and Src signaling, upon integrin engagement.

Main Methods:

  • Primary fibroblasts were infected with adenoviruses expressing Tac or Tac-beta1.
  • FAK and Src signaling activation was assessed by analyzing protein phosphorylation at specific tyrosine residues (Tyr-397 for FAK; Tyr-419 and Tyr-530 for Src).
  • Phosphorylation of Src substrates, p130Cas and paxillin, was examined to evaluate Src signaling downstream effects.

Main Results:

  • Tac-beta1 expression inhibited FAK activation by preventing phosphorylation at Tyr-397.
  • Src activation (phosphorylation at Tyr-419 and Tyr-530) remained unaffected by Tac-beta1.
  • Adhesion-induced tyrosine phosphorylation of p130Cas and paxillin was inhibited, indicating a block in Src signaling downstream of FAK.
  • Src-dependent signaling events were found to be FAK-dependent.

Conclusions:

  • Tac-beta1 inhibits cell spreading by preventing FAK phosphorylation at Tyr-397.
  • This inhibition disrupts the assembly of signaling complexes required for downstream Src substrate phosphorylation.
  • The findings suggest a critical role for FAK in mediating Src-dependent signaling essential for cell spreading.

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