Abstract
Bid plays an essential role in Fas-mediated apoptosis of the so-called type II cells. In these cells, following cleavage by caspase 8, the C-terminal fragment of Bid translocates to mitochondria and triggers the release of apoptogenic factors, thereby inducing cell death. Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. When phosphorylated, Bid was insensitive to caspase 8 cleavage in vitro. Moreover, a mutant of Bid that cannot be phosphorylated was found to be more toxic than wild-type Bid. Together, these data indicate that phosphorylation of Bid represents a new mechanism whereby cells control apoptosis.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Amino Acid Sequence
- Animals
- Apoptosis / physiology*
- BH3 Interacting Domain Death Agonist Protein
- Carrier Proteins / genetics
- Carrier Proteins / metabolism*
- Casein Kinase II
- Casein Kinases
- Caspase 8
- Caspase 9
- Caspases / metabolism*
- Cell Fractionation
- Cell Line
- DNA-Binding Proteins / metabolism
- Granzymes
- Humans
- Immunoblotting
- Mice
- Molecular Sequence Data
- Phosphorylation
- Protein Kinase Inhibitors
- Protein Kinases / isolation & purification
- Protein Kinases / metabolism*
- Protein Serine-Threonine Kinases / antagonists & inhibitors
- Protein Serine-Threonine Kinases / metabolism*
- Protein Structure, Tertiary
- Proto-Oncogene Proteins c-bcl-2 / metabolism
- Recombinant Proteins / genetics
- Recombinant Proteins / metabolism
- Serine Endopeptidases / metabolism
- fas Receptor / metabolism
Substances
- BH3 Interacting Domain Death Agonist Protein
- BID protein, human
- Bid protein, mouse
- Carrier Proteins
- DNA-Binding Proteins
- Protein Kinase Inhibitors
- Proto-Oncogene Proteins c-bcl-2
- Recombinant Proteins
- fas Receptor
- Protein Kinases
- Casein Kinase II
- Casein Kinases
- Protein Serine-Threonine Kinases
- GZMB protein, human
- Granzymes
- Gzmb protein, mouse
- Serine Endopeptidases
- CASP8 protein, human
- CASP9 protein, human
- Casp8 protein, mouse
- Casp9 protein, mouse
- Caspase 8
- Caspase 9
- Caspases