RIP2-β: 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-κB 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-1β 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-β, 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-β are associated with a loss of activation with respect to NF-κB and MAPK activation, IL-1β 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.