  Cellular signal transduction usually involves activation cascades, the
sequential activation of a series of proteins following the reception of an
input signal. Here we study the classic model of weakly activated cascades and
obtain analytical solutions for a variety of inputs. We show that in the
special but important case of optimal-gain cascades (i.e., when the
deactivation rates are identical) the downstream output of the cascade can be
represented exactly as a lumped nonlinear module containing an incomplete gamma
function with real parameters that depend on the rates and length of the
cascade, as well as parameters of the input signal. The expressions obtained
can be applied to the non-identical case when the deactivation rates are random
to capture the variability in the cascade outputs. We also show that cascades
can be rearranged so that blocks with similar rates can be lumped and
represented through our nonlinear modules. Our results can be used both to
represent cascades in computational models of differential equations and to fit
data efficiently, by reducing the number of equations and parameters involved.
In particular, the length of the cascade appears as a real-valued parameter and
can thus be fitted in the same manner as Hill coefficients. Finally, we show
how the obtained nonlinear modules can be used instead of delay differential
equations to model delays in signal transduction.
