Kinase’s Oscillatory Behavior Controls Cell Signaling

A key protein kinase enzyme participates in unusual oscillatory behavior that represents a new mechanism of signal transmission in cells. Andre Levchenko, Jin Zhang, and coworkers at Johns Hopkins University School of Medicine monitored signaling activity with fluorescence and used mechanistic modeling to show that protein kinase A, which helps regulate insulin secretion, calcium influx, and other important cellular processes, forms an oscillatory signaling circuit with cyclic adenosine monophosphate and Ca²⁺ in insulin-secreting cells (Nat. Chem. Biol., DOI: 10.1038/nchembio478). The circuit integrates diverse input signals by transducing them into different oscillatory frequencies and amplitudes, resulting in changes in cellular function. The study shows “that oscillatory patterns of activation allow protein kinase A to exercise effective spatially localized signaling control or switch to being a global regulator that can translocate into the nucleus and control gene expression,” Zhang says. The group believes such oscillatory systems might also exert spatiotemporal control over biological processes in other signaling networks and other types of cells.