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Phosphorylation of bid by casein kinases I and II regulates its cleavage by caspase 8

S Desagher1, A Osen-Sand, S Montessuit

  • 1CNRS UPR 9023, Montpellier, France. desagher@montp.inserm.fr

Molecular Cell
|October 5, 2001
PubMed

Insights

Bid phosphorylation by casein kinases I and II regulates Fas-mediated apoptosis in type II cells. This phosphorylation controls Bid cleavage by caspase 8, impacting cell death pathways.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Bid is crucial for Fas-mediated apoptosis in type II cells.
  • Caspase 8 cleaves Bid, initiating mitochondrial events and cell death.

Purpose of the Study:

  • To investigate the role of Bid phosphorylation in regulating Fas-mediated apoptosis.
  • To identify kinases involved in Bid phosphorylation.

Main Methods:

  • In vitro kinase assays using purified Bid and kinases.
  • Cell-based assays measuring apoptosis and Bid cleavage.
  • Site-directed mutagenesis to create non-phosphorylatable Bid mutants.

Main Results:

  • Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII).
  • Inhibition of CKI/CKII accelerated apoptosis and Bid cleavage; kinase hyperactivity delayed it.
  • Phosphorylated Bid was resistant to caspase 8 cleavage in vitro.
  • A non-phosphorylatable Bid mutant was more potent in inducing apoptosis.

Conclusions:

  • Bid phosphorylation by CKI and CKII is a novel regulatory mechanism in apoptosis.
  • This phosphorylation controls Bid's interaction with caspase 8, modulating cell death.
  • Understanding this pathway offers new insights into apoptosis control.

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