A Turn-On for Kinases

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Science  24 May 2013:
Vol. 340, Issue 6135, pp. 902-903
DOI: 10.1126/science.340.6135.902-d

Understanding of cellular regulatory mechanisms can be hindered by the inability to precisely control the activity of individual signaling components. Dagliyan et al. thus set out to create engineered protein kinases that could be activated by an exogenous ligand. They used the ligand-dependent protein-protein interaction between FKBP12 (12-kD FK506-binding protein) and FRB (FKBP12-rapamycin binding protein) that occurs in the presence of rapamycin. The goal was to confer ligand-dependent regulation in a manner that was generalizable to other proteins. Through a combination of rational design and trial and error, they were able to make a conformational switch module that allowed such control of several different protein kinases. Such a strategy is expected to help alleviate the challenges of elucidating the roles of individual components of complex cell regulatory circuits in vivo.

Proc. Natl. Acad. Sci. U.S.A. 110, 6800 (2013).

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