Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China.
Biophys Chem. 2010 Apr;147(3):130-9. doi: 10.1016/j.bpc.2010.01.004. Epub 2010 Jan 25.
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.
构建了一个整合的数学模型，该模型将支架蛋白纳入丝裂原活化蛋白激酶级联反应中。通过运用蒙特卡罗模拟，从理论上研究了支架蛋白对丝裂原活化蛋白激酶级联反应信号传递能力的调节特性。研究结果表明：（i）如果去磷酸化缓慢，支架结合会增加信号放大；如果去磷酸化迅速，放大作用会减弱。此外，随着支架数量的增加，如果去磷酸化缓慢，信号放大作用会减弱。（ii）支架数量可以控制激酶激活的时间，从而增强信号传递的时间灵活性。（iii）研究发现，对于缓慢去磷酸化的情况，支架会降低剂量反应曲线的陡度。对于快速去磷酸化的情况，增加支架数量会降低响应的高度，但分级响应的形状保持不变。此外，还阐明了我们研究结果的潜在机制及其与真实生物系统的相关性。
