Figure 1

Multisite phosphorylation and feedback structure. (a) This panel depicts the basic phosphorylation chain without feedback in which a target protein with J sites is phosphorylated by a kinase I and dephosphorylated by a phosphatase P. The ordered succession of phosphorylations yields J + 1 modification states, labelled 0, 1, ..., J. (b) The fully phosphorylated target protein relays a signal into pathways that eventually feed back on the phosphorylation chain. (c) Simplification of (b) in which the fully phosphorylated target protein acquires kinase activity and directly feeds back on the chain. We refer to this network configuration as the asymmetric circuit. (d) Schematic of the network with symmetric feedback in which the substrate protein is bifunctional, whereby the fully (de)phosphorylated form catalyzes (de)phosphorylation of its own precursors.