Construction of protocell-based artificial signal transduction pathway

Brain Morphology ◽

Transduction Pathway ◽

Cell Functions

Background: During aging and in age-associated disorders, such as Alzheimer's Disease (AD), learning abilities decline. Probably, disturbances in signal transduction in brain cells underlie the cognitive decline. The phosphorylation/dephosphorylation imbalance occurring in degenerating neurons was recently related to abnormal activity of one or more signal transduction pathways. AD is known to be associated with altered neuronal Ca2+ homeostasis, as Ca2+ accumulates in affected neurons leading to functional impairment. It is becoming more and more evident the involvement of signal transduction pathways acting upon Ca2+ metabolism and phosphorylation regulation of proteins. A growing interest raised around the role of signal transduction systems in a number of human diseases including neurodegenerative diseases, with special regard to the systems related to the phosphoinositide (PI) pathway and AD. The PI signal transduction pathway plays a crucial role, being involved in a variety of cell functions, such as hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking, ion channel activity, cytoskeleton regulation, cell cycle control, apoptosis, cell and tissue polarity, and contributes to regulate the Ca2+ levels in the nervous tissue. Conclusion: A number of observations indicated that PI-specific phospholipase C (PLC) enzymes might be involved in the alteration of neurotransmission. To understand the role and the timing of action of the signalling pathways recruited during the brain morphology changes during the AD progression might help to elucidate the aetiopathogenesis of the disease, paving the way to prognosis refinement and/or novel molecular therapeutic strategies.

Erythroid Differentiation Regulator 1 Strengthens TCR Signaling by Enhancing PLCγ1 Signal Transduction Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms23020844 ◽

2022 ◽

Vol 23 (2) ◽

pp. 844

Author(s):

Myun Soo Kim ◽

Dongmin Park ◽

Sora Lee ◽

Sunyoung Park ◽

Kyung Eun Kim ◽

...

Keyword(s):

Signal Transduction ◽

T Cells ◽

Cd4 T Cells ◽

Erythroid Differentiation ◽

Transduction Pathway ◽

Tcr Signaling ◽

Peripheral T Cells ◽

Signal Regulation

Erythroid differentiation regulator 1 (Erdr1) has previously been reported to control thymocyte selection via TCR signal regulation, but the effect of Erdr1 as a TCR signaling modulator was not studied in peripheral T cells. In this report, it was determined whether Erdr1 affected TCR signaling strength in CD4 T cells. Results revealed that Erdr1 significantly enhanced the anti-TCR antibody-mediated activation and proliferation of T cells while failing to activate T cells in the absence of TCR stimulation. In addition, Erdr1 amplified Ca2+ influx and the phosphorylation of PLCγ1 in CD4 T cells with the TCR stimuli. Furthermore, NFAT1 translocation into nuclei in CD4 T cells was also significantly promoted by Erdr1 in the presence of TCR stimulation. Taken together, our results indicate that Erdr1 positively modulates TCR signaling strength via enhancing the PLCγ1/Ca2+/NFAT1 signal transduction pathway.

CKA, a Novel Multidomain Protein, Regulates the JUN N-Terminal Kinase Signal Transduction Pathway in Drosophila

Molecular and Cellular Biology ◽

10.1128/mcb.22.6.1792-1803.2002 ◽

2002 ◽

Vol 22 (6) ◽

pp. 1792-1803 ◽

Cited By ~ 51

Author(s):

Hua-Wei Chen ◽

Maria Julia Marinissen ◽

Su-Wan Oh ◽

Xiu Chen ◽

Michael Melnick ◽

...

Keyword(s):

Signal Transduction ◽

Cell Sheet ◽

Leading Edge ◽

Genetic Screen ◽

Dorsal Closure ◽

Transduction Pathway ◽

Temporal Expression ◽

Multidomain Protein

ABSTRACT The Drosophila melanogaster JUN N-terminal kinase (DJNK) and DPP (decapentaplegic) signal transduction pathways coordinately regulate epithelial cell sheet movement during the process of dorsal closure in the embryo. By a genetic screen of mutations affecting dorsal closure in Drosophila, we have now identified a multidomain protein, connector of kinase to AP-1 (cka), that functions in the DJNK pathway and controls the localized expression of dpp in the leading-edge cells. We have also investigated how CKA acts. This unique molecule forms a complex with HEP (DJNKK), BSK (DJNK), DJUN, and DFOS. Complex formation activates BSK kinase, which in turn phosphorylates and activates DJUN and DFOS. These data suggest that CKA represents a novel molecule regulating AP-1 activity by organizing a molecular complex of kinases and transcription factors, thus coordinating the spatial-temporal expression of AP-1-regulated genes.

The Molecule Role Ontology: An Ontology for Annotation of Signal Transduction Pathway Molecules in the Scientific Literature

Comparative and Functional Genomics ◽

10.1002/cfg.432 ◽

2004 ◽

Vol 5 (6-7) ◽

pp. 528-536 ◽

Cited By ~ 8

Author(s):

Satoko Yamamoto ◽

Takao Asanuma ◽

Toshihisa Takagi ◽

Ken Ichiro Fukuda

Keyword(s):

Signal Transduction ◽

Scientific Literature ◽

Transduction Pathway ◽

Abstract Concepts ◽

Pathway Database ◽

Sequence Identity ◽

Concrete Objects ◽

Single Sequence

In general, it is not easy to specify a single sequence identity for each molecule name that appears in a pathway in the scientific literature. A molecule name may stand for concepts of various granularities, from concrete objects such as H-Ras and ERK1 to abstract concepts or categories such as Ras and MAPK. Typically, the relations among molecule names derive a hierarchical structure; without a proper way to handle this knowledge, it becomes ever more difficult to develop a reliable pathway database. This paper describes an ontology that is designed to annotate molecules in the scientific literature on signal transduction pathways.

Information transfer in mammalian glycan-based communication

10.1101/2021.05.10.443458 ◽

2021 ◽

Author(s):

Felix F Fuchsberger ◽

Dongyoon Kim ◽

Marten Kagelmacher ◽

Robert Wawrzinek ◽

Christoph Rademacher

Keyword(s):

Signal Transduction ◽

Cell Lines ◽

Information Transfer ◽

Cellular Heterogeneity ◽

Transduction Pathway ◽

Monocytic Cell ◽

Lectin Receptors ◽

Lectin Receptor

Glycan-binding proteins, so-called lectins, are exposed on mammalian cell surfaces and decipher the information encoded within glycans translating it into biochemical signal transduction pathways in the cell. These glycan-lectin communication pathways are complex and difficult to analyse. However, quantitative data with single cell resolution provides means to disentangle the associated signalling cascades. We chose C-Type lectin receptors (CLRs) expressed on immune cells as a model system to study their capacity to transmit information encoded in glycans of incoming particles. Lectin receptor NFκB-reporter cell lines expressing DC-SIGN, MCL, dectin-1, dectin-2, and mincle, as well as TNFαR and TLR-1&2 in monocytic cell lines were characterized by comparing their efficiency to transmit glycan-encoded information. The information content was measured by following NFκB dependent GFP expression. While most receptors did transmit information to NFκB efficiently, we found dectin-2 to be an inefficient signalling receptor. Yet upon closer analysis we show that the sensitivity of the dectin-2 signal transduction pathway (EC50) can be enhanced by overexpression of its co-receptor FcRγ, while its transmitted information cannot. In this context, we expanded our investigation towards the integration of multiple signal transduction pathways, which is crucial during pathogen recognition. We show how lectin receptors using a similar signal transduction pathway (dectin-1 and dectin-2) are being integrated; by striking a compromise between the lectins. By using dectin-2 and other lectins as example we demonstrate how cellular heterogeneity and the receptor itself determine the efficiency and therefore outcome of the signal transduction pathways.

Genetic analysis of the sevenless signal transduction pathway of Drosophila

Development ◽

10.1242/dev.119.supplement.41 ◽

1993 ◽

Vol 119 (Supplement) ◽

pp. 41-46 ◽

Cited By ~ 1

Author(s):

E. Hafen ◽

B. Dickson ◽

T. Raabe ◽

D. Brunner ◽

N. Oellers ◽

...

Keyword(s):

Signal Transduction ◽

Cell Fate ◽

Receptor Tyrosine Kinase ◽

Photoreceptor Cell ◽

Transduction Pathway ◽

Genetic Screens ◽

Constitutive Activation

The specification of the R7 photoreceptor cell fate in the developing eye of Drosophila depends on the local activation of the sevenless (sev) receptor tyrosine kinase (RTK) by boss, a protein expressed on the membrane of the neighboring R8 cell. Constitutive activation of the scv receptor results in a dosage dependent increase in the number of R7 cells per ommatidium. Genetic screens have been used to identify mutations that alter the efficiency of signal transduction. Subsequent molecular characterization of the corresponding genes has led to the identification of a number of proteins involved in transducing the signal from the receptor to the nucleus. In contrast to the receptor and its ligand, these components are shared between different signal transduction pathways not only in Drosophila but homologous components are also involved in signal transduction in other organisms.