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To elucidate the hidden dynamics of extracellular-signal-regulated kinase (ERK) signalling networks, we developed a simulation model of ERK signalling networks by constraining in silico dynamics based on in vivo dynamics in PC12 cells. We predicted and validated that transient ERK activation depends on rapid increases of epidermal growth factor and nerve(More)
Robust transmission of information despite the presence of variation is a fundamental problem in cellular functions. However, the capability and characteristics of information transmission in signaling pathways remain poorly understood. We describe robustness and compensation of information transmission of signaling pathways at the cell population level. We(More)
BACKGROUND Continuous NGF stimulation induces PC12 cell differentiation. However, why continuous NGF stimulation is required for differentiation is unclear. In this study, we investigated the underlying mechanisms of the timing-dependent requirement of NGF action for cell differentiation. METHODOLOGY/PRINCIPAL FINDINGS To address the timing-dependency of(More)
Transient responses of signaling molecules are seen in a wide variety of cellular processes that are mediated by distinct molecular mechanisms. Although transient responses might intuitively be thought to depend on the absolute concentration of growth factors or the intensity of stimulation, we here introduce that some transient responses are prompted by(More)
Ever since reversible protein phosphorylation was discovered, it has been clear that it plays a key role in the regulation of cellular processes. Proteins often undergo double phosphorylation, which can occur through two possible mechanisms: distributive or processive. Which phosphorylation mechanism is chosen for a particular cellular regulation bears(More)
BACKGROUND Modeling of cellular functions on the basis of experimental observation is increasingly common in the field of cellular signaling. However, such modeling requires a large amount of quantitative data of signaling events with high spatio-temporal resolution. A novel technique which allows us to obtain such data is needed for systems biology of(More)
A wide range of growth factors encode information into specific temporal patterns of MAP kinase (MAPK) and CREB phosphorylation, which are further decoded by expression of immediate early gene products (IEGs) to exert biological functions. However, the IEG decoding system remain unknown. We built a data-driven based on time courses of MAPK and CREB(More)
1 Data preprocessing The experimental data consist of hundreds of measurements at 24 time points. We average over all values at each time point and obtain a single time series for each of the molecular species, MAPKK and Mpp. We call these " the averaged data ". The MAPKK time series data will be used as an input to the models, and the Mpp data for(More)
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