The small GTPase ADP-ribosylation factor 6 (Arf6) plays pivotal roles in a wide variety of cellular events, including exocytosis, endocytosis, actin cytoskeleton reorganization and phosphoinositide metabolism, in various types of cells. To control such a wide variety of actions of Arf6, activation of Arf6 could be precisely controlled by its activators, guanine nucleotide exchange factors (GEFs), in spatial and temporal manners. In this manuscript, we summarize and discuss the characteristics of previously identified GEFs specific to Arf6 and activation machineries of Arf6.
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