An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.
Takanari Inoue, Won Do Heo, Joshua S Grimley, Thomas J Wandless, Tobias Meyer
Author Information
Takanari Inoue: Stanford University, Department of Molecular Pharmacology, Clark Center, 318 Campus Drive, Stanford, California 94305-5439, USA. jctinoue@stanford.edu
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.
References
Science. 1999 Mar 26;283(5410):2028-9
[PMID: 10206910]