scholarly journals Proteome-wide inference of protein kinase regulatory circuits

2019 ◽  
Author(s):  
Brandon M. Invergo ◽  
Borgthor Petursson ◽  
David Bradley ◽  
Girolamo Giudice ◽  
Evangelia Petsalaki ◽  
...  

SummaryComplex networks of regulatory relationships between protein kinases comprise a major component of intracellular signaling. Although many kinase-kinase regulatory relationships have been described in detail, these are biased towards well-studied kinases while the majority of possible relationships remains unexplored. Here, we implement data-driven, unbiased methods to predict human kinase-kinase regulatory relationships and whether they have activating or inhibiting effects. We incorporate high-throughput data, kinase specificity profiles, and structural information to produce our predictions. The results successfully recapitulate previously annotated regulatory relationships and can reconstruct known signaling pathways from the ground up. The full network of predictions is relatively sparse, with the vast majority of relationships assigned low probabilities. However, it nevertheless suggests denser modes of inter-kinase regulation than normally considered in intracellular signaling research.

2020 ◽  
Vol 6 (3) ◽  
pp. 573-581 ◽  
Author(s):  
Zhong-Hui Shen ◽  
Yang Shen ◽  
Xiao-Xing Cheng ◽  
Han-Xing Liu ◽  
Long-Qing Chen ◽  
...  

2018 ◽  
Author(s):  
Vered Raz ◽  
Yotam Raz ◽  
Davy van de Vijver ◽  
Davide Bindellini ◽  
Maaike van Putten ◽  
...  

Contractile properties of myofibers are dictated by the abundance of myosin heavy chain (MyHC) isoforms. MyHC composition designates muscle function and its alterations could unravel differential muscle involvement in muscular dystrophies and aging. Current analyses are limited to visual assessments in which myofibers expressing multiple MyHC isoforms are prone to misclassifications. As a result, complex patterns and subtle alterations are unidentified. We developed a high-throughput data-driven myofiber analysis to quantitatively describe the variations in myofibers across the muscle. We investigated alterations in myofiber composition between genotypes, two muscles and two age groups. We show that this analysis facilitates the discovery of complex myofiber compositions and its dependency on age, muscle type and genetic conditions.


2018 ◽  
Vol 33 (3) ◽  
pp. 4046-4053 ◽  
Author(s):  
Vered Raz ◽  
Yotam Raz ◽  
Davy Vijver ◽  
Davide Bindellini ◽  
Maaike Putten ◽  
...  

2015 ◽  
Author(s):  
Urszula Czerwinska ◽  
Laurence Calzone ◽  
Emmanuel Barillot ◽  
Andrei Zinovyev

Visualization and analysis of molecular profiling data together with biological networks are able to provide new mechanistical insights into biological functions. Currently, high-throughput data are usually visualized on top of predefined network layouts which are not always adapted to a given data analysis task. We developed a Cytoscape app which allows to construct biological network layouts based on the data from molecular profiles imported as values of nodes attributes. DeDaL is a Cytoscape 3.0 app which uses linear and non-linear algorithms of dimension reduction to produce data-driven network layouts based on multidimensional data (typically gene expression). DeDaL implements several data pre-processing and layout post-processing steps such as continuous morphing between two arbitrary network layouts and aligning one network layout with respect to another one by rotating and mirroring. Combining these possibilities facilitates creating insightful network layouts representing both structural network features and the correlation patterns in multivariate data. DeDaL is the first method allowing to construct biological network layouts from high-throughput data. DeDaL is freely available for downloading together with step-by-step tutorial at http://bioinfo-out.curie.fr/projects/dedal/.


2009 ◽  
Author(s):  
Yoshiki Katayama ◽  
Hirotaro Kitazaki ◽  
Jeong-Hun Kang ◽  
Xiaoming Han ◽  
Takeshi Mori ◽  
...  

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1443
Author(s):  
Yoshiaki Kamiyama ◽  
Sotaro Katagiri ◽  
Taishi Umezawa

Reversible phosphorylation is a major mechanism for regulating protein function and controls a wide range of cellular functions including responses to external stimuli. The plant-specific SNF1-related protein kinase 2s (SnRK2s) function as central regulators of plant growth and development, as well as tolerance to multiple abiotic stresses. Although the activity of SnRK2s is tightly regulated in a phytohormone abscisic acid (ABA)-dependent manner, recent investigations have revealed that SnRK2s can be activated by group B Raf-like protein kinases independently of ABA. Furthermore, evidence is accumulating that SnRK2s modulate plant growth through regulation of target of rapamycin (TOR) signaling. Here, we summarize recent advances in knowledge of how SnRK2s mediate plant growth and osmotic stress signaling and discuss future challenges in this research field.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Gerald Thiel ◽  
Tobias Schmidt ◽  
Oliver G. Rössler

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression.


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