The Intermolecular Interaction of Ephexin4 Leads to Autoinhibition by Impeding Binding of RhoG
AbstractEphexin4 is a guanine nucleotide-exchange factor (GEF) for RhoG and is involved in various RhoG-related cellular processes such as phagocytosis of apoptotic cells and migration of cancer cells. Ephexin4 forms an oligomer via an intermolecular interaction, and its GEF activity is increased in the presence of Elmo, an Ephexin4-interacting protein. However, it is uncertain if and how Ephexin4 is autoinhibited. Here, using an Ephexin4 mutant that abrogated the intermolecular interaction, we report that this interaction impeded binding of RhoG to Ephexin4 and thus inhibited RhoG activation. Mutation of the glutamate residue at position 295, which is a highly conserved residue located in the region of Ephexin4 required for the intermolecular interaction, to alanine (Ephexin4E295A) disrupted the intermolecular interaction and increased binding of RhoG, resulting in augmented RhoG activation. In addition, phagocytosis of apoptotic cells and formation of membrane ruffles were increased more by expression of Ephexin4E295A than by expression of wild-type Ephexin4. Taken together, our data suggest that Ephexin4 is autoinhibited through its intermolecular interaction, which impedes binding of RhoG. View Full-Text
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Kim, K.; Lee, J.; Moon, H.; Lee, S.-A.; Kim, D.; Yang, S.; Lee, D.-H.; Lee, G.; Park, D. The Intermolecular Interaction of Ephexin4 Leads to Autoinhibition by Impeding Binding of RhoG. Cells 2018, 7, 211.
Kim K, Lee J, Moon H, Lee S-A, Kim D, Yang S, Lee D-H, Lee G, Park D. The Intermolecular Interaction of Ephexin4 Leads to Autoinhibition by Impeding Binding of RhoG. Cells. 2018; 7(11):211.Chicago/Turabian Style
Kim, Kwanhyeong; Lee, Juyeon; Moon, Hyunji; Lee, Sang-Ah; Kim, Deokhwan; Yang, Susumin; Lee, Dae-Hee; Lee, Gwangrog; Park, Daeho. 2018. "The Intermolecular Interaction of Ephexin4 Leads to Autoinhibition by Impeding Binding of RhoG." Cells 7, no. 11: 211.
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