Recently, the importance of copper homeostasis has been moved into the forefront since copper has now been connected to several neurological diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and prion proteins. The key protein for maintenance of copper homeostasis in humans is Wilson's disease protein (Wndp). This protein, which is found in the brain and liver, is responsible for copper delivery to copper dependent proteins in the Trans Golgi Network and for the export of excess copper in the cell. It has been shown that phosphorylation is associated with the trafficking that leads to export of copper, but the mechanism of Wndp regulation by phosphorylation has not been shown. The goal of this proposed research is to decipher the role of copper dependent phosphorylation of Wndp in the cell and understand how this regulation contributes to copper homeostasis. Specifically, the phosphorylation site(s) on Wndp will be identified, the Wndp kinase will be isolated, and the effect of phosphorylation on trafficking and activity of Wndp will be evaluated.
| Bartee, Mee Y; Ralle, Martina; Lutsenko, Svetlana (2009) The loop connecting metal-binding domains 3 and 4 of ATP7B is a target of a kinase-mediated phosphorylation. Biochemistry 48:5573-81 |
| Bartee, Mee Y; Lutsenko, Svetlana (2007) Hepatic copper-transporting ATPase ATP7B: function and inactivation at the molecular and cellular level. Biometals 20:627-37 |
