β-arrestin1 mediates the endocytosis and functions of macrophage migration inhibitory factorβ-arrestin1介导的内吞作用和功能,巨噬细胞迁移抑制因子.pdfVIP

b-Arrestin1 Mediates the Endocytosis and Functions of Macrophage Migration Inhibitory Factor 1,2. 1,2. 1 1 Lishi Xie , Xiaohang Qiao , Yanfang Wu , Jie Tang * 1 Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People’s Republic of China, 2 Graduate University, Chinese Academy of Sciences, Beijing, People’s Republic of China Abstract Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, regulating inflammatory and immune responses. MIF binds to cell surface receptor CD74, resulting in both rapid and sustained ERK activation. It was reported that MIF-induced rapid ERK activation requires its co-receptor CD44. But the exact mechanism underlying sustained ERK activation is not well understood. In the current study, we described a detailed mechanism of MIF mediated sustained ERK activation. We found that b-arrestin1, a scaffold protein involved in the activation of the MAPK cascade, interacts with CD74 upon MIF stimulation, resulting in CD74-mediated MIF endocytosis in a chlorpromazine (CPZ)-sensitive manner. b-arrestin1 is also involved in endocytotic MIF signaling, leading to sustained ERK activation. Therefore b-arrestin1 plays a central role in coupling MIF endocytosis to sustained ERK activation. Citation: Xie L, Qiao X, Wu Y, Tang J (2011) b-Arrestin1 Mediates the Endocytosis and Functions of Macrophage Migration Inhibitory Factor. PLoS ONE 6(1): e16428. doi:10.1371/journal.pone.0016428 Editor: David Holowka, Cornell University, United States of America Received September 29, 2010; Accepted December 16, 2010; Published January 25, 2011 Copyright: 2011 Xie et al. This is an open-access article distributed under the terms of the Creative Commons Attribu