An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways |
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Authors: | Inoue Takanari Heo Won Do Grimley Joshua S Wandless Thomas J Meyer Tobias |
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Institution: | Stanford University, Department of Molecular Pharmacology, Clark Center, 318 Campus Drive, Stanford, California 94305-5439, USA. jctinoue@stanford.edu |
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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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