Statistics of cellular signal transduction as a race to the nucleus by multiple random walkers in compartment/phosphorylation space

@article{citeulike:2838457, abstract = {Cellular signal transduction often involves a reaction network of phosphorylation and transport events arranged with a ladder topology. If we keep track of the location of the phosphate groups describing an abstract state space, a simple model of signal transduction involving enzymes can be mapped on to a problem of how multiple biased random walkers compete to reach their target in the nucleus yielding a signal. Here, the first passage time probability and the survival probability for multiple walkers can be used to characterize the response of the network. The statistics of the first passage through the network has an asymmetric distribution with a long tail arising from the hierarchical structure of the network. This distribution implies a significant difference between the mean and the most probable signal transduction time. The response patterns for various external inputs generated by our model agree with recent experiments. In addition, the model predicts that there is an optimal phosphorylation enzyme concentration for rapid signal transduction. 10.1073/pnas.0607698103}, author = {Lu, Ting and Shen, Tongye and Zong, Chenghang and Hasty, Jeff and Wolynes, Peter G. }, citeulike-article-id = {2838457}, doi = {10.1073/pnas.0607698103}, journal = {Proceedings of the National Academy of Sciences}, keywords = {analysis, phosphorylation, scl, signal, statistics, transduction}, month = {November}, number = {45}, pages = {16752--16757}, posted-at = {2008-05-28 01:07:14}, priority = {2}, title = {Statistics of cellular signal transduction as a race to the nucleus by multiple random walkers in compartment/phosphorylation space}, url = {http://dx.doi.org/10.1073/pnas.0607698103}, volume = {103}, year = {2006} }

TY - JOUR ID - citeulike:2838457 L3 - citeulike-article-id:2838457 TI - Statistics of cellular signal transduction as a race to the nucleus by multiple random walkers in compartment/phosphorylation space JF - Proceedings of the National Academy of Sciences VL - 103 IS - 45 SP - 16752 EP - 16757 N2 - Cellular signal transduction often involves a reaction network of phosphorylation and transport events arranged with a ladder topology. If we keep track of the location of the phosphate groups describing an abstract state space, a simple model of signal transduction involving enzymes can be mapped on to a problem of how multiple biased random walkers compete to reach their target in the nucleus yielding a signal. Here, the first passage time probability and the survival probability for multiple walkers can be used to characterize the response of the network. The statistics of the first passage through the network has an asymmetric distribution with a long tail arising from the hierarchical structure of the network. This distribution implies a significant difference between the mean and the most probable signal transduction time. The response patterns for various external inputs generated by our model agree with recent experiments. In addition, the model predicts that there is an optimal phosphorylation enzyme concentration for rapid signal transduction. 10.1073/pnas.0607698103 KW - analysis KW - phosphorylation KW - scl KW - signal KW - statistics KW - transduction AU - Lu, Ting AU - Shen, Tongye AU - Zong, Chenghang AU - Hasty, Jeff AU - Wolynes, Peter PY - 2006/11/07/ UR - http://dx.doi.org/10.1073/pnas.0607698103 ER -