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Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration
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Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration
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Journal Article
Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration
2016
Overview
The small GTPase Rac1 has been implicated in the formation and dissemination of tumours. Upon activation by guanine nucleotide exchange factors (GEFs), Rac1 associates with a variety of proteins in the cell thereby regulating various functions, including cell migration. However, activation of Rac1 can lead to opposing migratory phenotypes raising the possibility of exacerbating tumour progression when targeting Rac1 in a clinical setting. This calls for the identification of factors that influence Rac1-driven cell motility. Here we show that Tiam1 and P-Rex1, two Rac GEFs, promote Rac1 anti- and pro-migratory signalling cascades, respectively, through regulating the Rac1 interactome. In particular, we demonstrate that P-Rex1 stimulates migration through enhancing the interaction between Rac1 and the actin-remodelling protein flightless-1 homologue, to modulate cell contraction in a RhoA-ROCK-independent manner.
The small GTPase Rac1 regulates various cellular processes, including cell migration. However, Rac1 can have opposing migratory effects. Here the authors show that two guanine nucleotide exchange factors, Tiam1 and P-Rex1, differentially regulate the Rac1 interactome to determine the downstream phenotype.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/19
/ 14/32
/ 14/63
/ 38/89
/ 82/51
/ 82/58
/ 82/80
/ 96/34
/ Animals
/ Cancer
/ Carrier Proteins - metabolism
/ Guanine Nucleotide Exchange Factors - genetics
/ Guanine Nucleotide Exchange Factors - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Motility
/ Proteins
/ rac1 GTP-Binding Protein - genetics
/ rac1 GTP-Binding Protein - metabolism
/ Science
