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Phosphoinositide 3-kinases (PI3Ks) and Ras and Rho family small GTPases are key regulators of cell polarization, motility, and chemotaxis. They influence each other's activities by direct and indirect feedback processes that are only partially understood. Here, we show that 21 small GTPase homologs activate PI3K. Using a microscopy-based binding assay, we(More)
Cellular networks are composed of complicated interconnections among components, and some subnetworks of particular functioning are often identified as network motifs. Among such network motifs, feedback loops are thought to play important dynamical roles. Intriguingly, such feedback loops are very often found as a coupled structure in cellular circuits.(More)
Regulator of calcineurin 1 (RCAN1) is a key regulator of the calcineurin-NFAT signaling network in organisms ranging from yeast to human, but its functional role is still under debate because different roles of RCAN1 have been suggested under various experimental conditions. To elucidate the mechanisms underlying the RCAN1 regulatory system, we used a(More)
Biological oscillations are found ubiquitously in cells and are widely variable, with periods varying from milliseconds to months, and scales involving subcellular components to large groups of organisms. Interestingly, independent oscillators from different cells often show synchronization that is not the consequence of an external regulator. What is the(More)
In RNA virus-infected cells, retinoic acid-inducible gene-I-like receptors (RLRs) sense foreign RNAs and activate signaling cascades to produce IFN-α/β. However, not every infected cell produces IFN-α/β that exhibits cellular heterogeneity in antiviral immune responses. Using the IFN-β-GFP reporter system, we observed bimodal IFN-β production in the(More)
MOTIVATION Spatio-temporal regulation of gene expression is an indispensable characteristic in the development processes of all animals. 'Master switches', a central set of regulatory genes whose states (on/off or activated/deactivated) determine specific developmental fate or cell-fate specification, play a pivotal role for whole developmental processes.(More)
MOTIVATION Gene regulatory networks (GRNs) govern cellular differentiation processes and enable construction of multicellular organisms from single cells. Although such networks are complex, there must be evolutionary design principles that shape the network to its present form, gaining complexity from simple modules. RESULTS To isolate particular design(More)
E. coli has two-component systems composed of histidine kinase proteins and response regulator proteins. For a given extracellular stimulus, a histidine kinase senses the stimulus, autophosphorylates and then passes the phosphates to the cognate response regulators. The histidine kinase in an orthodox two-component system has only one histidine domain where(More)
Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties? We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling network. Our results show that the human signaling network can(More)
The identification of network motifs has been widely considered as a significant step towards uncovering the design principles of biomolecular regulatory networks. To date, time-invariant networks have been considered. However, such approaches cannot be used to reveal time-specific biological traits due to the dynamic nature of biological systems, and hence(More)