PUBLICATION

RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis

Authors
Inohara, N., del Peso, L., Koseki, T., Chen, S., and Nunez, G.
ID
ZDB-PUB-030902-2
Date
1998
Source
The Journal of biological chemistry   273(20)(erratum: J. Biol. Chem. 273(29):18675): 12296-12300 (Journal)
Registered Authors
Inohara, Naohiro
Keywords
none
MeSH Terms
  • Adenosine Triphosphate/metabolism
  • Amino Acid Sequence
  • Apoptosis*
  • Binding Sites
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Cysteine Endopeptidases/metabolism*
  • DNA, Complementary
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Molecular Sequence Data
  • Mutagenesis
  • Protein Binding
  • Protein Kinases/chemistry
  • Protein Kinases/genetics
  • Protein Kinases/metabolism*
  • Proteins/metabolism*
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • fas Receptor/metabolism*
PubMed
9575181 Full text @ J. Biol. Chem.
Abstract
Signaling through the CD95/Fas/APO-1 death receptor plays a critical role in the homeostasis of the immune system. RICK, a novel protein kinase that regulates CD95-mediated apoptosis was identified and characterized. RICK is composed of an N-terminal serine-threonine kinase catalytic domain and a C-terminal region containing a caspase-recruitment domain. RICK physically interacts with CLARP, a caspase-like molecule known to bind to Fas-associated protein with death domain (FADD) and caspase-8. Expression of RICK promoted the activation of caspase-8 and potentiated apoptosis induced by Fas ligand, FADD, CLARP, and caspase-8. Deletion mutant analysis revealed that both the kinase domain and caspase-recruitment domain were required for RICK to promote apoptosis. Significantly, expression of a RICK mutant in which the lysine of the putative ATP-binding site at position 38 was replaced by a methionine functioned as an inhibitor of CD95-mediated apoptosis. Thus, RICK represents a novel kinase that may regulate apoptosis induced by the CD95/Fas receptor pathway.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping