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 r ole in the homeostasis of the immune system, RICK, a novel protein kin ase that regulates CD95-mediated apoptosis was identified and characte rized. RICK is composed of an N-terminal serine-threonine kinase catal ytic domain and a C-terminal region containing a caspase-recruitment d omain, RICK physically interacts with CLARP, a caspase-like molecule k nown to bind to Fas-associated protein with death domain (FADD) and ca spase-8. Expression of RICK promoted the activation of caspase-8 and p otentiated apoptosis induced by Fas ligand, FADD, CLARP, and caspase-8 . Deletion mutant analysis revealed that both the kinase domain and ca spase-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 repr esents a novel kinase that may regulate apoptosis induced by the CD95/ Fas receptor pathway.