scholarly journals A Cell-Signaling Network Temporally Resolves Specific versus Promiscuous Phosphorylation

Cell Reports ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. 1202-1214 ◽  
Author(s):  
Evgeny Kanshin ◽  
Louis-Philippe Bergeron-Sandoval ◽  
S. Sinan Isik ◽  
Pierre Thibault ◽  
Stephen W. Michnick
Keyword(s):  
Cell Signaling ◽  
Signaling Network ◽  
A Cell

scholarly journals Systematic calibration of a cell signaling network model

2010 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyoung Ae Kim ◽  
Sabrina L Spencer ◽  
John G Albeck ◽  
John M Burke ◽  
Peter K Sorger ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Network Model ◽  
Signaling Network ◽  
A Cell

scholarly journals Profiling Cell Signaling Networks at Single-cell Resolution

2020 ◽  
Vol 19 (5) ◽  
pp. 744-756 ◽  
Author(s):  
Xiao-Kang Lun ◽  
Bernd Bodenmiller
Keyword(s):  
Cell Signaling ◽  
Single Cell ◽  
Signaling Network ◽  
Signaling Networks ◽  
Network Heterogeneity ◽  
Network Analyses ◽  
Cell Measurement ◽  
A Cell ◽  
Cell Signaling Networks ◽  
Many Sources

Signaling networks process intra- and extracellular information to modulate the functions of a cell. Deregulation of signaling networks results in abnormal cellular physiological states and often drives diseases. Network responses to a stimulus or a drug treatment can be highly heterogeneous across cells in a tissue because of many sources of cellular genetic and non-genetic variance. Signaling network heterogeneity is the key to many biological processes, such as cell differentiation and drug resistance. Only recently, the emergence of multiplexed single-cell measurement technologies has made it possible to evaluate this heterogeneity. In this review, we categorize currently established single-cell signaling network profiling approaches by their methodology, coverage, and application, and we discuss the advantages and limitations of each type of technology. We also describe the available computational tools for network characterization using single-cell data and discuss potential confounding factors that need to be considered in single-cell signaling network analyses.

Protein Flexibility Catalyzes a Cell Signaling Reaction of the Ras-GAP Complex

2019 ◽  
Author(s):  
Keiei Kumon ◽  
Masahiro Higashi ◽  
Shinji Saito ◽  
Shigehiko Hayashi
Keyword(s):  
Cell Signaling ◽  
Conformational Changes ◽  
Catalytic Reaction ◽  
Protein Complex ◽  
Enzyme Mechanism ◽  
Activation Free Energy ◽  
Chemical Catalysis ◽  
Simple Chemical ◽  
A Cell ◽  
Enzyme Molecules

Many enzyme molecules exhibit characteristic global and slow dynamics which furnish them with allostery realizing remarkable molecular functionalities more than simple chemical catalysis. However, molecular mechanism of a catalytic reaction associated with the molecular flexibility of enzymes is not well-understood. Here we report a hybrid molecular simulation study on GTPase activity of a Ras-GAP protein complex for cell signaling termination. We unveiled that extensive conformational changes of the protein complex and exclusion of internal water molecules are induced upon the transition state (TS) formation in the catalytic reaction and significantly lower the reaction activation free energy. We also revealed that tumor-related mutations perturb those conformational changes upon the TS formation, leading to reduction of the catalytic activity. The findings of the remarkably dynamic protein conformation directly linking to the catalytic reaction have broad implications for understanding of enzyme mechanism and for developments of allosteric drugs and novel catalysts.

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