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Dephosphorylation of Fas-ligand and caveolin-1 is a prerequisite step in Fas-ligand - caveolin-1 complex formation

Xenia A Glukhova1, Julia A Trizna1, Olga V Proussakova1

  • 1Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Puschino, Institutskaya st., 3, 142290, Russia.

Cellular Signalling
|February 29, 2020
PubMed

Insights

Dephosphorylation of Fas-ligand and caveolin-1 is critical for triggering Fas-mediated cell death. This study reveals that dephosphorylation allows Fas-ligand to bind caveolin-1, initiating apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Fas-ligand (CD178) is a TNF family protein that induces cell death.
  • Previous work established the necessity of Fas-ligand and caveolin-1 interaction for Fas-ligand-mediated cell death.
  • The role of Fas-ligand and caveolin-1 phosphorylation in their association and cell death induction was unknown.

Purpose of the Study:

  • To investigate the role of Fas-ligand and caveolin-1 phosphorylation in their physical association.
  • To elucidate the mechanism by which phosphorylation state influences Fas-mediated cell death induction.

Main Methods:

  • Analysis of protein-protein interactions using co-immunoprecipitation.
  • Assessment of protein phosphorylation states using Western blotting with phospho-specific antibodies.
  • Evaluation of cell death induction using cell viability assays.
  • Pharmacological inhibition of kinases and phosphatases.

Main Results:

  • In control cells, Fas-ligand and caveolin-1 are phosphorylated and do not interact; Fas-ligand complexes with p59Fyn-kinase.
  • Upon cell death activation, p59Fyn-kinase expression/activity decreases, leading to Fas-ligand dephosphorylation and complex formation with caveolin-1.
  • Phosphorylation of Fas-ligand and caveolin-1 on tyrosine residues suppresses Fas-mediated cell death.

Conclusions:

  • Dephosphorylation of Fas-ligand and caveolin-1 is essential for the formation of the Fas-ligand-caveolin-1 complex.
  • This dephosphorylation event is critical for the activation of the Fas-ligand-mediated apoptotic pathway and subsequent cell death execution.
Keywords:
Caveolin-1Cell deathFas-ligandTyrosine phosphorylationp59Fyn-kinase

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