Open AccessFour‐dimensional dynamics of MAPK information‐processing systems
Author(s) -
Kholodenko Boris N.,
Birtwistle Marc R.
Publication year - 2009
Publication title -
wiley interdisciplinary reviews: systems biology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.087
H-Index - 51
eISSN - 1939-005X
pISSN - 1939-5094
DOI - 10.1002/wsbm.16
Subject(s) - mapk/erk pathway , protein kinase a , microbiology and biotechnology , xenopus , phosphatase , phosphorylation , kinase , mapk cascade , signal transduction , biology , chemistry , biochemistry , gene
Mitogen‐activated protein kinase (MAPK) cascades process a myriad of stimuli received by cell‐surface receptors and generate precise spatiotemporal guidance for multiple target proteins, dictating receptor‐specific cellular outcomes. Computational modeling reveals that the intrinsic topology of MAPK cascades enables them to amplify signal sensitivity and amplitude, reduce noise, and display intricate dynamic properties, which include toggle switches, excitation pulses, and oscillations. Specificity of signaling responses can be brought about by signal‐induced feedback and feedforward wiring imposed on the MAPK cascade backbone. Intracellular gradients of protein activities arise from the spatial separation of opposing reactions in kinase‐phosphatase cycles. The membrane confinement of the initiating kinase in MAPK cascades and cytosolic localization of phosphatases can result in precipitous gradients of phosphorylated signal‐transducers if they spread solely by diffusion. Endocytotic trafficking of active kinases driven by molecular motors and traveling waves of protein phosphorylation can propagate phosphorylation signals from the plasma membrane to the nucleus, especially in large cells, such as Xenopus eggs. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models