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Developmental Dynamics : An Official... Sep 2017Signal transduction through multiple distinct pathways regulates and orchestrates the numerous biological processes comprising heart development. This review outlines... (Review)
Review
Signal transduction through multiple distinct pathways regulates and orchestrates the numerous biological processes comprising heart development. This review outlines the roles of the FGFR, EGFR, Wnt, BMP, Notch, Hedgehog, Slit/Robo, and other signaling pathways during four sequential phases of Drosophila cardiogenesis-mesoderm migration, cardiac mesoderm establishment, differentiation of the cardiac mesoderm into distinct cardiac cell types, and morphogenesis of the heart and its lumen based on the proper positioning and cell shape changes of these differentiated cardiac cells-and illustrates how these same cardiogenic roles are conserved in vertebrates. Mechanisms bringing about the regulation and combinatorial integration of these diverse signaling pathways in Drosophila are also described. This synopsis of our present state of knowledge of conserved signaling pathways in Drosophila cardiogenesis and the means by which it was acquired should facilitate our understanding of and investigations into related processes in vertebrates. Developmental Dynamics 246:641-656, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Cell Differentiation; Drosophila; Drosophila Proteins; Gene Expression Regulation, Developmental; Heart; Signal Transduction
PubMed: 28598558
DOI: 10.1002/dvdy.24530 -
Current Opinion in Cell Biology Feb 1996Small GTP-binding proteins of the Rho family appear to integrate extracellular signals from diverse receptor types and initiate rearrangements of F-actin. Active members... (Review)
Review
Small GTP-binding proteins of the Rho family appear to integrate extracellular signals from diverse receptor types and initiate rearrangements of F-actin. Active members of the Rho family, Rho and Rac, are now joined by Cdc42 which induces filopodia. Downstream of the Rho family proteins, actin polymerization may be induced by an increase in the availability of actin filament barbed ends. Actin organization may be affected by exposure of actin-binding sites on proteins such as vinculin and ezrin.
Topics: Actins; Signal Transduction
PubMed: 8791404
DOI: 10.1016/s0955-0674(96)80050-0 -
The Biochemical Journal Jun 2022In health and disease, liver cells are continuously exposed to cytokines and growth factors. While individual signal transduction pathways induced by these factors were...
In health and disease, liver cells are continuously exposed to cytokines and growth factors. While individual signal transduction pathways induced by these factors were studied in great detail, the cellular responses induced by repeated or combined stimulations are complex and less understood. Growth factor receptors on the cell surface of hepatocytes were shown to be regulated by receptor interactions, receptor trafficking and feedback regulation. Here, we exemplify how mechanistic mathematical modelling based on quantitative data can be employed to disentangle these interactions at the molecular level. Crucial is the analysis at a mechanistic level based on quantitative longitudinal data within a mathematical framework. In such multi-layered information, step-wise mathematical modelling using submodules is of advantage, which is fostered by sharing of standardized experimental data and mathematical models. Integration of signal transduction with metabolic regulation in the liver and mechanistic links to translational approaches promise to provide predictive tools for biology and personalized medicine.
Topics: Liver; Models, Biological; Models, Theoretical; Signal Transduction; Systems Biology
PubMed: 35748700
DOI: 10.1042/BCJ20210548 -
American Journal of Physiology. Cell... May 2023More and more computational techniques have been applied to model biological systems, especially signaling pathways in medical systems. Due to the large number of... (Review)
Review
More and more computational techniques have been applied to model biological systems, especially signaling pathways in medical systems. Due to the large number of experimental data driven by high-throughput technologies, new computational concepts have been developed. Nevertheless, often the necessary kinetic data cannot be determined in sufficient number and quality because of experimental complexity or ethical reasons. At the same time, the number of qualitative data drastically increased, for example, gene expression data, protein-protein interaction data, and imaging data. Especially for large-scale models, the application of kinetic modeling techniques can fail. On the other hand, many large-scale models have been constructed applying qualitative and semiquantitative techniques, for example, logical models or Petri net models. These techniques make it possible to explore system's dynamics without knowing kinetic parameters. Here, we summarize the work of the last 10 years for modeling signal transduction pathways in medical applications applying Petri net formalism. We focus on analysis techniques based on system's invariants without any kinetic parameters and show predictions of all signaling pathways of the system. We start with an intuitive introduction into Petri nets and system's invariants. We illustrate the main concepts using the tumor necrosis factor receptor 1 (TNFR1)-induced nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) pathway as a case study. Summarizing recent models, we discuss the advantages and challenges of Petri net applications to medical signaling systems. In addition, we provide exemplarily interesting Petri net applications to model signaling in medical systems of the last years that use the well-known stochastic and kinetic concepts developed about 50 years ago.
Topics: Algorithms; Computer Simulation; Signal Transduction; Models, Biological; Receptor Protein-Tyrosine Kinases
PubMed: 36878844
DOI: 10.1152/ajpcell.00487.2022 -
Current Opinion in Structural Biology Aug 2019Optical induction of intracellular signaling by membrane-associated and integral membrane proteins allows spatiotemporally precise control over second messenger... (Review)
Review
Optical induction of intracellular signaling by membrane-associated and integral membrane proteins allows spatiotemporally precise control over second messenger signaling and cytoskeletal rearrangements that are important to cell migration, development, and proliferation. Optogenetic membrane recruitment of a protein-of-interest to control its signaling by altering subcellular localization is a versatile means to these ends. Here, we summarize the signaling characteristics and underlying structure-function of RGS-LOV photoreceptors as single-component membrane recruitment tools that rapidly, reversibly, and efficiently carry protein cargo from the cytoplasm to the plasma membrane by a light-regulated electrostatic interaction with the membrane itself. We place the technology-relevant features of these recently described natural photosensory proteins in context of summarized protein engineering and design strategies for optically controlling membrane protein signaling.
Topics: Allosteric Regulation; Cell Membrane; Optogenetics; Signal Transduction
PubMed: 30884362
DOI: 10.1016/j.sbi.2019.01.017 -
Journal of Hepatology Nov 2021A balanced increase in DNA content (ploidy) is observed in some human cell types, including bone-resorbing osteoclasts, platelet-producing megakaryocytes, cardiomyocytes... (Review)
Review
A balanced increase in DNA content (ploidy) is observed in some human cell types, including bone-resorbing osteoclasts, platelet-producing megakaryocytes, cardiomyocytes or hepatocytes. The impact of increased hepatocyte ploidy on normal physiology and diverse liver pathologies is still poorly understood. Recent findings suggest swift genetic adaptation to hepatotoxic stress and the protection from malignant transformation as beneficial effects. Herein, we discuss the molecular mechanisms regulating hepatocyte polyploidisation and its implication for different liver diseases and hepatocellular carcinoma. We report on centrosomes' role in limiting polyploidy by activating the p53 signalling network (via the PIDDosome multiprotein complex) and we discuss the role of this pathway in liver disease. Increased hepatocyte ploidy is a hallmark of hepatic inflammation and may play a protective role against liver cancer. Our evolving understanding of hepatocyte ploidy is discussed from the perspective of its potential clinical application for risk stratification, prognosis, and novel therapeutic strategies in liver disease and hepatocellular carcinoma.
Topics: Humans; Liver; Liver Neoplasms; Polyploidy; Prognosis; Signal Transduction
PubMed: 34228992
DOI: 10.1016/j.jhep.2021.06.030 -
RNA Biology May 2021The innate immune system relies on a germ-line-encoded repertoire of pattern recognition receptors (PRRs), activated by deeply conserved pathogen signatures, such as... (Review)
Review
The innate immune system relies on a germ-line-encoded repertoire of pattern recognition receptors (PRRs), activated by deeply conserved pathogen signatures, such as bacterial cell wall components or foreign nucleic acids. To enable effective defence against invading pathogens and prevent from deleterious inflammation, PRR-driven immune responses are tightly controlled by a dense network of nuclear and cytoplasmic regulators. Long non-coding RNAs (lncRNAs) are increasingly recognized as important components of these regulatory circuitries, providing positive and negative control of PRR-induced innate immune responses. The present review provides an overview of the presently known roles of lncRNAs in human and murine innate antiviral and antibacterial immunity. The emerging roles in host defence and inflammation suggest that further mechanistic insights into the cellular functions of lncRNAs will decisively advance our molecular understanding of immune-associated diseases and open new avenues for therapeutic intervention.
Topics: Animals; Humans; Immunity, Innate; Inflammation; Mice; RNA, Long Noncoding; Signal Transduction
PubMed: 33138685
DOI: 10.1080/15476286.2020.1845505 -
BMB Reports Mar 2018The Hippo signaling pathway controls nuclear accumulation and stability of the transcriptional coregulator YAP and its paralog TAZ. The activity of Hippo-YAP signaling... (Review)
Review
The Hippo signaling pathway controls nuclear accumulation and stability of the transcriptional coregulator YAP and its paralog TAZ. The activity of Hippo-YAP signaling is influenced not only by biochemical signals, but also by cell shape and mechanical tension transmitted through cell-cell junctions and cell-matrix adhesions. Data accumulated thus far indicates that the actin cytoskeleton is a key mediator of the regulation of Hippo-YAP signaling by means of a variety of biochemical and mechanical cues. In this review, we have outlined the role of actin dynamics and actin-associated proteins in the regulation of Hippo-YAP signaling. In addition, we discuss actinmediated regulation of YAP/TAZ activity independent of the core Hippo kinases MST and LATS. Although our understanding of the link between Hippo-YAP signaling and the actin cytoskeleton is progressing rapidly, many open questions remain. [BMB Reports 2018; 51(3): 151-156].
Topics: Actin Cytoskeleton; Actins; Animals; Hippo Signaling Pathway; Humans; Mechanotransduction, Cellular; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 29353600
DOI: 10.5483/bmbrep.2018.51.3.012 -
Pain Physician 2011
Topics: Animals; Humans; Inflammation; Inflammation Mediators; Pain; Signal Transduction
PubMed: 21267046
DOI: No ID Found -
International Review of Neurobiology 2014Addiction is due to changes in the structure and function of the brain, including neuronal networks and the cells that comprise them. Within cells, gene expression... (Review)
Review
Addiction is due to changes in the structure and function of the brain, including neuronal networks and the cells that comprise them. Within cells, gene expression changes can track and help explain their altered function. Transcriptional changes induced by addictive agents are dynamic and divergent and range from signal pathway-specific perturbations to widespread molecular and cellular dysregulation that can be measured by "omic" methods and that can be used to identify new pathways. The molecular effects of addiction depend on timing of exposure or withdrawal, the stage of adaptation, the brain region, and the behavioral model, there being many models of addiction. However, the molecular neural adaptations across different drug exposures, conditions, and regions are to some extent shared and can reflect common actions on pathways relevant to addiction. Epigenetic studies of DNA methylation and histone modifications and studies of regulatory RNA networks have been informative for elucidating the mechanisms of transcriptional change in the addicted brain.
Topics: Animals; Brain; Gene Expression; Gene Expression Regulation; Gene Regulatory Networks; Humans; Signal Transduction; Substance-Related Disorders
PubMed: 25172478
DOI: 10.1016/B978-0-12-801105-8.00010-2