RIP2-beta: a novel alternative mRNA splice variant of the receptor interacting protein kinase RIP2.
RIP2/RICK/CARDIAK is a member of the receptor interacting protein kinase (RIP) family. RIP2 promotes NF-kappaB activation as well as activation of the MAPKs JNK, ERK1/2 and p38 MAPK, thereby playing an emergent role in the innate immune response and NOD signaling. Moreover, RIP2 has been shown to interact with the CARD of caspase-1 and to induce IL-1beta maturation as well as in the induction of CD95-mediated programmed cell death by enhancing caspase-8 activity. Here, we report the identification and characterization of a novel alternative mRNA splice variant of RIP2, encoding a protein designated RIP2-beta, comprised of only a portion of the N-terminal kinase domain and lacking the intermediate region and C-terminal CARD. As revealed by gene transfer experiments, these structural changes in RIP2-beta are associated with a loss of activation with respect to NF-kappaB and MAPK activation, IL-1beta secretion, and caspase-8-mediated apoptosis. In conclusion, alternative mRNA splicing may be involved in the regulation of RIP2 actions, underlying the complexity of RIP2-dependent pathways regulating stress signaling and apoptosis.
Krieg
Andreas
A
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Le Negrate
Gaëlle
G
Reed
John C
JC
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D020928:Mitogen-Activated Protein Kinases; D053181:Caspase 8