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?-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 ?-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. ?-arrestin1 is also involved in endocytotic MIF signaling, leading to sustained ERK activation. Therefore ?-arrestin1 plays a central role in coupling MIF endocytosis to sustained ERK activation.

SUBMITTER: Xie L 

PROVIDER: S-EPMC3026819 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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β-Arrestin1 mediates the endocytosis and functions of macrophage migration inhibitory factor.

Xie Lishi L   Qiao Xiaohang X   Wu Yanfang Y   Tang Jie J  

PloS one 20110125 1


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-arre  ...[more]

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