Tools for reconstituting intracellular signaling networks

The Schultz group develops tools for imaging and for modulating cellular enzyme activities in the context of intracellular signal transduction networks. While most research groups are developing enzyme or receptor inhibitors to modulate signaling networks, we are particularly interested in activating events downstream of the receptor level. By using total synthesis, we generated a set of membrane-permeant lipid derivatives. The compounds are equipped with bioactivatable protecting groups for non-invasive cell entry and intracellular deprotection. New aspects of growth factor receptor signaling including phosphoinositide-regulated entry of the recycling versus the lysosomal endocytotic pathway will be presented. For improved temporal and spatial control, the first membrane-permeant photoactivatable phosphoinositide derivatives will be introduced and the use of these compounds as discovery tools will be detailed. Finally, to activate enzyme activities, we employed chemical dimerizer techniques. Here, the first independent activation of small trimeric G-protein subunits and the effect on intracellular calcium signaling monitored on the microscopy stage will be detailed.