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Sci. STKE, 11 May 2004
Vol. 2004, Issue 232, p. tw164
[DOI: 10.1126/stke.2322004TW164]

EDITORS' CHOICE

IMMUNOLOGY β-Arrestin2 as Linker of Immune and Nervous Systems

The sympathetic nervous system is known to influence immune responses, but the molecular mechanisms by which these regulatory systems are connected are not fully understood. Gao et al. now propose that β-arrestin2 may function to link signals from β2-adrenergic receptor (β2AR) (which is known to be expressed in various cells of the immune system) to regulation of NF-{kappa}B, the transcription factor that functions as a central mediator of innate and adaptive immune responses. They made the unanticipated connection when I{kappa}Bα (the NF-{kappa}B inhibitor that is phosphorylated and degraded in response to signals that activate NF-{kappa}B-dependent transcription) turned up in a yeast two-hybrid screen for proteins interacting with β-arrestin2. Immunoprecipitation studies confirmed the interaction of the endogenous proteins in human embryonic kidney HEK 293 cells. Treatment of cells with tumor necrosis factor-α normally causes degradation of I{kappa}Bα, but overexpression of β-arrestin2 blunted this response. Furthermore, stimulation of the β2ARs increased interaction of β-arrestin2 and I{kappa}Bα and reduced expression of NF-{kappa}B target genes. β-Arrestin derives its name from its originally described function to negatively regulate GPCRs [heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors] by promoting desensitization and internalization of activated receptors. More recent evidence has revealed positive signaling roles for the proteins, and the work of Gao et al. implicates β-arrestin in directly linking the immune responses to signals generated by the sympathetic nervous systems.

H. Gao, Y. Sun, Y. Wu, B. Luan, Y. Wang, B. Qu, G. Pei, Identification of β-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-{kappa}B pathways. Mol. Cell 14, 303-317 (2004). [Online Journal]

Citation: β-Arrestin2 as Linker of Immune and Nervous Systems. Sci. STKE 2004, tw164 (2004).


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