Hua Gao 1, Yue Sun 1, Yalan Wu, Bing Luan, Yaya Wang, Bin Qu and Gang Pei
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, People's Republic of China
1 These authors contributed equally to this work.
Molecular Cell, 2004, 14: 303-317
Abstract
Norepinephrine released by the sympathetic nerve terminals regulates the immune system primarily via its stimulation of 2-adrenergic receptor (2AR), but the underlying molecular mechanisms remain to be elicited. 2AR, a well-studied G protein-coupled receptor (GPCR), is functionally regulated by -arrestin2, which not only causes receptor desensitization and internalization but also serves as a signaling molecule in GPCR signal transduction. Here we show that -arrestin2 directly interacts with IB (inhibitor of NF-B, the key molecule in innate and adaptive immunity) and thus prevents the phosphorylation and degradation of IB. Consequently, -arrestin2 effectively modulates activation of NF-B and expression of NF-B target genes. Moreover, stimulation of 2AR significantly enhances -arrestin2-IB interaction and greatly promotes -arrestin2 stabilization of IB, indicating that -arrestin2 mediates a crosstalk between 2AR and NF-B signaling pathways. Taken together, the current study may present a novel mechanism for regulation of the immune system by the sympathetic nervous system.
Corresponding author. Correspondence: Gang Pei, 86-21-54921371 (phone), 86-21-54921011 (fax) | 
