The Effects Of Phosphorylation Rocessive Mechanism On Dynamics Of MAPK Signal Transdution Pathway

Growth, development and reproduction of multicellular organisms depend not only on the material and energy metabolism of the cells, but also depend on extensive and accurate cell-cell communication and signal transduction. Signal transduction pathway is that the receptors of cell surface receive and identify the various stimulations, then transmit signals through signaling pathways, causing physiological and biochemical effects. The mitogen-acivated protein kinase signaling (MAPK pathway) is an important and typical signaling pathway in so many signaling transduction pathways, a series of highly conserved kinase’s and phosphatase’s phosphorylation and dephosphorylation transmit the cell external signals which accepted by activated Ras protein to the downstream, to produce the intracellular appropriate responses.There are two ways to describe the kinetics mechanism of the phosphorylation and dephosphorylation:distributive mechanism and processive mechanism. Many existing studies use distributive mechanism to describe the dynamic mechanism of the MAPK transduction pathway model. Recently, an experimental result shows that the kinetics mechanism of the MAPK cascade in mammalian cells can convert distributive phosphorylation into the processive phosphorylation under certain conditions. This confirms that the processive phosphorylation is an important mechanism of protein phosphorylation and dephosphorylation in MAPK signal transduction pathway. Molecular crowded and scaffolding protein et al are the reasons.The theoretical work studying on the phosphorylation processive mechanism is few and it is not clear that the effects of phosphorylation processive mechanism on dynamics of MAPK signal transduction pathway. In order to solve these problems, a theoretical model about phosphorylation processive mechanism has been constructed in this paper, the main research works and achievements are as follows:First of all, the kinetics of model of a two sites phosphorylation and dephosphorylation processive mechanism was deduced, according to the Michaelis-Menten kinetic mechanism. And the mechanism of action was applied to the MAPK cascade, to get a mathematical description of the action mechanism of the MAPK cascade.Secondly, different dynamic mechanisms are applied to the MAPK signal transduction pathway model controlled by different feedbacks. The main research is that the kinase’s and phosphatase’s processive action mechanisms in the homogeneous system and heterogeneous system and how the degree of the processivity impact MAPK signal transduction pathway. The results showed that:kinase phosphorylation processively is most conducive to the spread of the signal, the strength the processively phosphorylation of the phosphatase greatest impact on the transfer of the MAPK signaling.Last, binding the regulation of calcium oscillation frequency to M APK cascades, we integrated calcium oscillation model, Ras-GTPase cycle model and the MAPK cascade model in a homogeneous system. In theory, we analyzed that the effect of the processive mechanism on the calcium oscillation frequency control ppMAPK’s negative correlation, and we compared the theoretical results with the experimental results of Sabine Kupzig.