A new function of ATP—beyond its passive roles as an energy source and a phosphate donor for phosphorylation reactions—was unraveled by Jefferson researchers.
Their studies revealed a new model of kinase regulation, whereby ATP modulates an “on-off-switch” mechanism in Akt by inducing conformational changes in the Akt kinase domain.
The three members of the Akt protein kinase family play key roles in multiple cellular processes, including glucose metabolism, cell survival and proliferation, and cell migration. The Jefferson team’s data was reported in the Proceedings of the National Academy of Sciences (PNAS) and was the subject of a perspective in Science Signaling in their May issue, entitled “Uncaging Akt.”
Jefferson paper’s senior author Tung O. Chan, Ph.D., assistant professor at Jefferson’s Center for Translational Medicine and Ulrich Rodeck, M.D., Ph.D., professor at the Department of Dermatology and Cutaneous Biology, indicate that their work, together with a complimentary study by Genentech researchers, describes a new mechanism with high translational appeal.
A molecular switch that affects the activation state of specific Akt isoforms may be exploited to modulate Akt signal strength in malignant diseases, as well as in diabetes and diseases of the heart and the central nervous system.
The Jefferson studies were conducted by a team of investigators at the Center for Translational Medicine, Department of Medicine and Kimmel Cancer Center, in collaboration with colleagues in the Departments of Dermatology and Cutaneous Biology, Radiation Oncology, Molecular Biology and Biochemistry, and Pharmaceutical Sciences.