RIP2beta: Identifikation und Charakterisierung einer neuen alternativen Spleißvariante der Receptor Interacting Protein Kinase RIP2

Abstract

RIP2 is a member of the receptor interacting protein kinase (RIP) family. RIP2 activates NF-kappaB as well as the MAP-Kinases JNK, ERK1/2 and p38 MAPK, thereby playing an emergent role in the regulation of the innate immune response and NOD signalling cascade. In addition, RIP2 has been shown to induce CD95-mediated apoptosis via stimulation of caspase-8 and to induce IL-1beta secretion by activating caspase-1. By performing a BLAST search, we identified a novel splice variant of RIP2 (RIP2beta) characterized by the loss of exon 2, encoding a protein with extensive truncation of the kinase domain and lacking the intermediate region and C-terminal CARD. Using RT-PCR analysis RIP2 variants were differentially expressed in a variety of human cell lines. Whereas the classical isoform RIP2alpha exhibited a strong homodimerization via its CARD and kinase domain, RIP2beta failed to oligomerize. Moreover, the deletion of the kinase domain in RIP2beta was associated with a loss in autophosphorylation. In contrast to RIP2alpha, RIP2beta failed to activate NF-kappaB and MAPK, IL-1beta secretion, and caspase-8-mediated apoptosis.