title: β-Arrestin1 mediates the endocytosis and functions of macrophage migration inhibitory factor.
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 β-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. β-arrestin1 is also involved in endocytotic MIF signaling, leading to sustained ERK activation. Therefore β-arrestin1 plays a central role in coupling MIF endocytosis to sustained ERK activation.
authors.affiliation: Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Lishi
authors.initials: L
authors.lastname: Xie
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Qiao
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D019390:Arrestins / Q000502:physiology*; D002460:Cell Line; D004705:Endocytosis; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000502:physiology*; D051379:Mice; D000071557:beta-Arrestins
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D019390:Arrestins; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D000071557:beta-Arrestins; C045084:invariant chain; D048049:Extracellular Signal-Regulated MAP Kinases