RIP2-beta: a novel alternative mRNA splice variant of the receptor interacting protein kinase RIP2.

Abstract:

: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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Krieg A,Le Negrate G,Reed JC

doi

10.1016/j.molimm.2008.11.002

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

1163-70

issue

6

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(08)00752-9

journal_volume

46

pub_type

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