System identification reveals temporal decoding systems of MAP kinase and CREB phosphorylation by selective IEG expression.

We made a system identification of temporal decoding of MAP kinase and CREB phosphorylation by selective immediate early genes expression such as c-FOS, EGR1, c-JUN and JUNB using time series data and the nonlinear ARX model. We found that the expression of IEGs has a distinct upstream dependency, and there are distinct switch-like responses and temporal filters for decoding upstream signals. For example, pulsatile ERK phosphorylation was decoded by selective expression of EGR1 rather than c-FOS, and conjunctive NGF and PACAP stimulation was decoded by synergistic JUNB expression through a switch-like response to c-FOS.