Erhart, Dominik. Control of cellular signals in time and space. 2012, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_9781
In this PhD thesis we developed of a novel heterodimerization system based on protein tags devoid of endogenous signaling counterparts. Extensive structure modifications of these dimerizers in a pharmacochemical manner afforded highly cell permeable molecules that can dimerize proteins intracellularly. With the control of these molecules we now are not only able to dimerize any protein of interest, but can also target them to any selected cellular compartment.
Utilizing this ability to target proteins to specific cellular domains, we could demonstrate that the dimerizer induced translocation of effector proteins to the plasma membrane led to a subsequent activation of downstream targets. This was shown by the translocation of the iSH2 domain of the regulatory subunit p85 of PI3K to the plasma membrane and the activation of the PI3K/PKB/mTOR pathway. In contrast to receptor ligand induced multiple pathway activation, our system has the power of a molecular button, activating single signaling cascades without affecting others. The presented small molecule-induced heterodimerization system is suitable to selectively control signaling pathways in time and space, without affecting endogenous signaling systems.
|Advisors:||Wymann, Matthias Paul|
|Committee Members:||Johnsson, Kai|
|Faculties and Departments:||03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Cancer- and Immunobiology (Wymann)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||156 S.|
|Last Modified:||30 Jun 2016 10:48|
|Deposited On:||27 Mar 2012 14:18|
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