Rip2: A Key Molecule that Regulates both Innate and Acquired Immunity
Arnold I. Chin,
Paul W. Dempsey,
The Receptor interacting protein-2 (Rip2, also called RICK, CARDIAK) is an intracellular serine-threonine kinase that contains a carboxy-terminal caspase activation and recruitment domain (CARD). The initial biochemical analysis emphasized a role for Rip2 in the activation of nuclear factor-kappaB (NF-kB) and apoptosis when overexpressed. The subsequent generation of mice with a targeted deletion of the gene for Rip2 and the description of a possible target for Rip2 kinase activity has clarified the role of Rip2. Following infectious challenges, the activation of a protective immune response relies on the coordinated interplay of contextual stimulation and inflammatory processes. All mammals must balance the need to combat dangerous pathogens from the destructive potential for mistaking autologous cells or proteins as appropriate targets for response. Rip2 has carved out an evolutionary niche serving as a regulator of inflammatory responses. Rip2 helps to direct or propagate signals towards cell-mediated immune responses and resolution of infection by modifying signals from pathogen recognition receptors (PRRs) such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (Nod) family members of innate immunity, the T cell receptor (TCR) complex of acquired immunity, and cytokine signaling of the interleukin (IL)-1 receptor family and IL-12 signaling pathways. Here we wish to outline the progress made in describing the biological significance of Rip2 and the mode of regulation of this kinase. Further studies considering Rip2 as a target of intervention have the potential to be of great clinical value.
Keywords: immune system, natural killer (nk) cell, cytokine, lymphocytes, antigen, lipopolysaccharide, protein kinase receptor
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