A generic model for open signaling cascades with forward activation

Abstract

In this work, cellular signal transduction in an open cascade with forward activation was studied. By proposing a generic model which captures the common features of major existing models in the literature, it is showed how signaling profile changes during the propagation along the cascade. In particular, a typical OFF-ON-OFF switch-like transient behavior with prolonged temporary ON state is revealed, where OFF and ON represent the states of low level and high level concentrations, respectively. Analytically this phenomenon is closely related to uniform convergence of the active protein concentration of downstream cycles in the finite time range and its failure in the entire time domain. Consequently a classification of open signaling cascade which can sustain OFF-ON-OFF behavior in the far downstream cycles is accessible. Relevant biological issues, such as delayed activation of downstream reaction cycles, signal amplification and prolonged signal duration, to the generic model is discussed.