hahn lab

engineered small molecule responses

under construction


Engineered allosteric activation by rapamycin or its non-immunosuppressive analogs
(RapR Src, RapR Fyn, RapR Yes, RapR Lyn, RapR FAK, RapR p38, uniRapR Src, uniRapR FAK, uniRapR p38)

Kinases are activated upon addition of rapamycin (or a non-immunosuppressive analog) to the cell medium. An engineered domain is inserted in the kinase at a highly conserved site, rendering the kinase inactive until rapamycin is added. This can be applied to other kinases using the approach described in the methods article below. Kinases can now be activated by inserting a single rapamycin-responsive domain (uniRapR) but originally depended upon co-expression of the kinase analog and a second protein (RapR). Kinases published as RapR analogs can be converted to uniRapR analogs (see methods article).


Example Application


Methods Article


Upon activation a kinase interacts with one specific downstream target
(RapR TAP Src-p130Cas, RapR TAP Src-Fak)

The kinase is modified so that it is activated by rapamycin, and requires interaction with a specific downstream target for activation:


Control the rapamycin-mediated methods above with light

We have used a 'caged' analog of rapamycin, an analog whose activity is blocked by a photocleavable protecting group, to confer 'light control' on the rapamycin-mediated methods above.


Methods Article




back to tools & reagents page

Home | People | Alumni | Publications | Tools & Reagents | Cell Cinema | Links | Contacts | Join Us | Webmaster | ©2011 UNC Department of Pharmacology