Theoretical study for regulatory property of scaffold protein on MAPK cascade: A qualitative modeling

An integrated mathematical model, which incorporates scaffold proteins into a mitogen-activated protein kinases cascade, is constructed. By employing Monte Carlo simulation, regulatory property of scaffold protein on signaling ability for the mitogen-activated protein kinases cascade is investigated theoretically. It is found that (i) scaffold binding increases signal amplification if dephosphorylation is slow and decreases amplification if dephosphorylation is rapid. Also, increasing the number of scaffold decreases amplification if dephosphorylation is slow. (ii) The scaffold number can control the timing of kinase activation so that the time flexibility of signaling is enhanced. (iii) It is observed that for slow dephosphorylation case, scaffolds decrease the sharpness of the dose-response curves. While for fast dephosphorylation case, increasing scaffold number decreases the height of response, but the shape of graded response is sustained. Furthermore, the underlying mechanism and the correlation of our results with real biological systems are clarified.