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Dorothea Fiedler

Dorothea Fiedler

Thu, Oct. 30, 2014, 4:30pm - 6:00pm
Frick Chemistry Laboratory, Taylor Auditorium

The inositol pyrophosphates provide a link between metabolism and signaling

By integrating signaling cues with metabolic status, cells are able to modulate a range of processes according to their internal resources. The diphosphoinositol polyphosphates (PP-IPs) are a unique group of messengers that control glucose uptake and energy homeostasis, and provide an important link between signaling and metabolic networks. It is thought that PP-IPs exert their pleiotropic effects as allosteric small molecule regulators and via pyrophosphorylation of protein substrates, but most details in PP-IP signaling have remained elusive due to a paucity of suitable reagents.

Our group is taking chemical approaches to elucidate the molecular mechanisms in PP-IP signaling.  We have designed non-hydrolyzable PP-IP bisphosphonate analogues and have utilized these analogs for the affinity purification of inositol polyphosphate binding proteins. In parallel, we devised a method that provides easy access to pyrophosphopeptides. The pyrophosphopeptides were subsequently employed for the development specific enrichment procedures and for mass spectrometry-based detection of pyrophosphoproteins. Overall, our data support a central role for the inositol pyrophosphates at the interface of signaling and metabolism and contribute significantly to a better understanding of the complex PP-IP signaling landscape.