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An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways
Authors:Inoue Takanari  Heo Won Do  Grimley Joshua S  Wandless Thomas J  Meyer Tobias
Institution:Stanford University, Department of Molecular Pharmacology, Clark Center, 318 Campus Drive, Stanford, California 94305-5439, USA. jctinoue@stanford.edu
Abstract:We made substantial advances in the implementation of a rapamycin-triggered heterodimerization strategy. Using molecular engineering of different targeting and enzymatic fusion constructs and a new rapamycin analog, Rho GTPases were directly activated or inactivated on a timescale of seconds, which was followed by pronounced cell morphological changes. As signaling processes often occur within minutes, such rapid perturbations provide a powerful tool to investigate the role, selectivity and timing of Rho GTPase-mediated signaling processes.
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