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.
Citation
Inohara, N., del Peso, L., Koseki, T., Chen, S., and Nunez, G. (1998) RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. The Journal of biological chemistry. 273(20)(erratum: J. Biol. Chem. 273(29):18675):12296-12300.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping