Working out how the GSK3 enzyme prevents blood clotting

Identification of the molecular targets by which glycogen synthase kinase 3 regulates human platelet function and thrombosis

Dr Ingeborg Hers and colleagues at the University of Bristol are working out how an enzyme, called GSK3, prevents blood clotting. Platelets are small blood cells that play a crucial role in causing blood clots to form within arteries, a process called thrombosis, which can lead to heart attacks and strokes. When platelets become activated, they clump together to form a blood clot. Scientists have discovered that a protein called GSK3 plays an important role in preventing this process. We know that when it is stimulated, GSK3 induces a chemical change called phosphorylation, in proteins in the platelet cells. But we don’t yet know which proteins are phosphorylated by GSK3 and are responsible for blocking platelet activation. In this project, Dr Hers will use different approaches to identify the platelet proteins that are phosphorylated by GSK3. She will investigate which ones block platelet function and ultimately could prevent thrombosis. This research will help us understand how platelets are activated and may reveal new ways of managing thrombosis and heart disease.