  We propose a model of parameter learning for signal transduction, where the
objective function is defined by signal transmission efficiency. We apply this
to learn kinetic rates as a form of evolutionary learning, and look for
parameters which satisfy the objective. This is a novel approach compared to
the usual technique of adjusting parameters only on the basis of experimental
data. The resulting model is self-organizing, i.e. perturbations in protein
concentrations or changes in extracellular signaling will automatically lead to
adaptation. We systematically perturb protein concentrations and observe the
response of the system. We find compensatory or co-regulation of protein
expression levels. In a novel experiment, we alter the distribution of
extracellular signaling, and observe adaptation based on optimizing signal
transmission. We also discuss the relationship between signaling with and
without transients. Signaling by transients may involve maximization of signal
transmission efficiency for the peak response, but a minimization in
steady-state responses. With an appropriate objective function, this can also
be achieved by concentration adjustment. Self-organizing systems may be
predictive of unwanted drug interference effects, since they aim to mimic
complex cellular adaptation in a unified way.
