Phosphorylation by protein kinase CK2: a signaling switch for the caspase-inhibiting protein ARC

Mol Cell. 2002 Aug;10(2):247-58. doi: 10.1016/s1097-2765(02)00600-7.

Abstract

Caspases play a central role in apoptosis, but their activity is under the control of caspase-inhibiting proteins. A characteristic of caspase-inhibiting proteins is direct caspase binding. It is yet unknown how the localization of caspase-inhibiting proteins is regulated and whether there are upstream signals controlling their function. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm. Our results reveal a molecular mechanism by which a caspase-inhibiting protein requires phosphorylation in order to prevent apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Casein Kinase II
  • Caspase 8
  • Caspase 9
  • Caspase Inhibitors*
  • Caspases / metabolism
  • Cell Line
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Mitochondria / metabolism
  • Muscle, Skeletal / metabolism
  • Myocardium / cytology
  • Myocardium / metabolism
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein Binding
  • Protein Transport
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction*
  • Time Factors

Substances

  • Caspase Inhibitors
  • Cytoskeletal Proteins
  • DISC1 protein, human
  • Disc1 protein, rat
  • Immediate-Early Proteins
  • Nerve Tissue Proteins
  • activity regulated cytoskeletal-associated protein
  • Phosphotyrosine
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • CASP8 protein, human
  • CASP9 protein, human
  • Casp8 protein, rat
  • Casp9 protein, rat
  • Caspase 8
  • Caspase 9
  • Caspases