A generic model for open signaling cascades with forward activation (Q455779)

The paper deals with a generic model for cellular signal transduction in an open cascade with forward activation. This model is intended to cover the features of many existing models in the literature. The cycles considered in the model are single phosphorylation-dephosphorylation cycles. The uniform convergence of the signaling profile is studied in both finite and infinite time. It is shown that in finite time the uniform convergence holds for any nonnegative external stimulus, not necessarily a continuous one. For infinite time, sufficient conditions on the external stimulus which guarantee the uniform convergence are provided. Some numerical examples are provided. Closely related to the uniform convergence is the OFF-ON-OFF switch-like transient phenomenon (that is, the phenomenon exhibiting rapid dynamical transitions between OFF and ON states after a temporary stay at either of them), which is discussed here. The obtained results are illustrated here on some existing models (the weakly activated model of Heinrich and Chaves, the linear rates model of Heinrich and Grubelnik, the GK model of Goldbeter and Koshland, the multi-step phosphorylation model of Qu and Vondriska, and othere GK-like models), by showing that similar dynamics arise about the asymptotic signaling profile. At the end of the paper, the author discusses some biological issues arising from the generic model, such as delayed activation of downstrean-reaction cycles, signal amplification and prolonged signal duration.