biostudies-literatureUnknown106(5)Sun JThe processive phosphorylation mechanism becomes important when there is macromolecular crowding in the cytoplasm. Integrating the processive phosphorylation mechanism with the traditional distributive one, we propose a mixed dual-site phosphorylation (MDP) mechanism in a single-layer phosphorylation cycle. Further, we build a degree model by applying the MDP mechanism to a three-layer mitogen-activated protein kinase (MAPK) cascade. By bifurcation analysis, our study suggests that the crowded-environment-induced pseudoprocessive mechanism can qualitatively change the response of this biological network. By adjusting the degree of processivity in our model, we find that the MAPK cascade is able to switch between the ultrasensitivity, bistability, and oscillatory dynamical states. SensitiviBiophysical journal1215-26https://www.ebi.ac.uk/biostudies/studies/S-EPMC4026786biostudies-literatureEnhancement of tunability of MAPK cascade due to coexistence of processive and distributive phosphorylation mechanisms.PMC4026786Ding YYang LYi MJia YWei WSun JfalseEnhancement of tunability of MAPK cascade due to coexistence of processive and distributive phosphorylation mechanisms.The processive phosphorylation mechanism becomes important when there is macromolecular crowding in the cytoplasm. Integrating the processive phosphorylation mechanism with the traditional distributive one, we propose a mixed dual-site phosphorylation (MDP) mechanism in a single-layer phosphorylation cycle. Further, we build a degree model by applying the MDP mechanism to a three-layer mitogen-activated protein kinase (MAPK) cascade. By bifurcation analysis, our study suggests that the crowded-environment-induced pseudoprocessive mechanism can qualitatively change the response of this biological network. By adjusting the degree of processivity in our model, we find that the MAPK cascade is able to switch between the ultrasensitivity, bistability, and oscillatory dynamical states. Sensitivi2014-01-01T00:00:00Z2014 Mar2025-04-04T08:42:29.243Z2019-03-27T01:28:32ZS-EPMC40267862460694510.1016/j.bpj.2014.01.036