title: An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.
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.
authors.affiliation: Stanford University, Department of Molecular Pharmacology, Clark Center, 318 Campus Drive, Stanford, California 94305-5439, USA. jctinoue@stanford.edu
authors.forename: Takanari
authors.initials: T
authors.lastname: Inoue
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Grimley
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wandless
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors; D007700:Kinetics; D051379:Mice; D041681:NIH 3T3 Cells; D015202:Protein Engineering / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology*; D014178:Translocation, Genetic / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; D020741:rho GTP-Binding Proteins; D020123:Sirolimus