Intrinsic Feedbacks in MAPK Signaling Cascades Lead to Bistability and Oscillations

Abstract

Previous studies have demonstrated that double phosphorylation of a protein can lead to bistability if some conditions are fulfilled. It was also shown that the signaling behavior of a covalent modification cycle can be quantitatively and, more importantly, qualitatively modified when this cycle is coupled to a signaling pathway as opposed to being isolated. This property was named retroactivity. These two results are studied together in this paper showing the existence of interesting phenomena--oscillations and bistability--in signaling cascades possessing at least one stage with a double-phosphorylation cycle as in MAPK cascades.