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

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.

Pubmed ID: 9575181 RIS Download

Mesh terms: Adenosine Triphosphate | Amino Acid Sequence | Antigens, CD95 | Apoptosis | Binding Sites | CASP8 and FADD-Like Apoptosis Regulating Protein | Cysteine Endopeptidases | DNA, Complementary | Humans | Intracellular Signaling Peptides and Proteins | Molecular Sequence Data | Mutagenesis | Protein Binding | Protein Kinases | Proteins | Receptor-Interacting Protein Serine-Threonine Kinase 2 | Sequence Deletion | Sequence Homology, Amino Acid