scholarly journals Protease-Activated Receptors: A Means of Converting Extracellular Proteolysis into Intracellular Signals

IUBMB Life ◽  
2002 ◽  
Vol 53 (6) ◽  
pp. 277-281 ◽  
Author(s):  
E. J. Mackie ◽  
C. N. Pagel ◽  
R. Smith ◽  
M. R. de Niese ◽  
S.- J. Song ◽  
...  
2008 ◽  
Vol 100 (09) ◽  
pp. 483-488 ◽  
Author(s):  
Chiwaka Kimura ◽  
Masahiro Oike

SummaryThrombin induces Ca2+ transients and subsequent nitric oxide (NO) production in vascular endothelial cells. Thrombin cleaves protease-activated receptors, resulting in activation of intracellular signals, but it is not clarified how the extracellular thrombin stays around the cells to exert its enzyme activities. This study aimed to investigate the possible involvement of heparin sulfate proteoglycan (HSPG) in the effects of thrombin on vascular endothelium. Heparinase III completely removed the polysaccharide chain of HSPG in bovine aortic endothelial cells (BAECs).Thrombin induced Ca2+ transients in control BAECs, but not in heparinase III-treated BAECs. In contrast, ATP induced Ca2+ transients both in control and heparinase III-treated BAECs. Thrombin that was pre-incubated with heparin also failed to induced Ca2+ transients in BAECs. Furthermore, thrombin-induced NO production, as assessed with DAF-2 flu-orescence, was suppressed in heparinase III-treated BAECs and by the pre-incubation of thrombin with heparin. ATP-induced NO production was, however, not affected in heparinase III-treated BAECs. These results indicate that it is essential for thrombin to bind to the polysaccharide chain of HSPG for inducing Ca2+ transients and NO production in BAECs.


2020 ◽  
Vol 48 (2) ◽  
pp. 613-620
Author(s):  
Clara Ortegón Salas ◽  
Katharina Schneider ◽  
Christopher Horst Lillig ◽  
Manuela Gellert

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.


2001 ◽  
Vol 120 (5) ◽  
pp. A114-A114
Author(s):  
C GAO ◽  
H HU ◽  
S LIU ◽  
N GAO ◽  
Y XIA ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 229
Author(s):  
Yoshie Umehara ◽  
Chanisa Kiatsurayanon ◽  
Juan Valentin Trujillo-Paez ◽  
Panjit Chieosilapatham ◽  
Ge Peng ◽  
...  

Itch or pruritus is the hallmark of atopic dermatitis and is defined as an unpleasant sensation that evokes the desire to scratch. It is also believed that itch is a signal of danger from various environmental factors or physiological abnormalities. Because histamine is a well-known substance inducing itch, H1-antihistamines are the most frequently used drugs to treat pruritus. However, H1-antihistamines are not fully effective against intractable itch in patients with atopic dermatitis. Given that intractable itch is a clinical problem that markedly decreases quality of life, its treatment in atopic dermatitis is of high importance. Histamine-independent itch may be elicited by various pruritogens, including proteases, cytokines, neuropeptides, lipids, and opioids, and their cognate receptors, such as protease-activated receptors, cytokine receptors, Mas-related G protein-coupled receptors, opioid receptors, and transient receptor potential channels. In addition, cutaneous hyperinnervation is partly involved in itch sensitization in the periphery. It is believed that dry skin is a key feature of intractable itch in atopic dermatitis. Treatment of the underlying conditions that cause itch is necessary to improve the quality of life of patients with atopic dermatitis. This review describes current insights into the pathophysiology of itch and its treatment in atopic dermatitis.


Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2256
Author(s):  
Serenella Nardi ◽  
Michela Schiavon ◽  
Ornella Francioso

Humic substances (HS) are dominant components of soil organic matter and are recognized as natural, effective growth promoters to be used in sustainable agriculture. In recent years, many efforts have been made to get insights on the relationship between HS chemical structure and their biological activity in plants using combinatory approaches. Relevant results highlight the existence of key functional groups in HS that might trigger positive local and systemic physiological responses via a complex network of hormone-like signaling pathways. The biological activity of HS finely relies on their dosage, origin, molecular size, degree of hydrophobicity and aromaticity, and spatial distribution of hydrophilic and hydrophobic domains. The molecular size of HS also impacts their mode of action in plants, as low molecular size HS can enter the root cells and directly elicit intracellular signals, while high molecular size HS bind to external cell receptors to induce molecular responses. Main targets of HS in plants are nutrient transporters, plasma membrane H+-ATPases, hormone routes, genes/enzymes involved in nitrogen assimilation, cell division, and development. This review aims to give a detailed survey of the mechanisms associated to the growth regulatory functions of HS in view of their use in sustainable technologies.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Claude Lormeau ◽  
Fabian Rudolf ◽  
Jörg Stelling

AbstractCells can encode information about their environment by modulating signaling dynamics and responding accordingly. Yet, the mechanisms cells use to decode these dynamics remain unknown when cells respond exclusively to transient signals. Here, we approach design principles underlying such decoding by rationally engineering a synthetic short-pulse decoder in budding yeast. A computational method for rapid prototyping, TopoDesign, allowed us to explore 4122 possible circuit architectures, design targeted experiments, and then rationally select a single circuit for implementation. This circuit demonstrates short-pulse decoding through incoherent feedforward and positive feedback. We predict incoherent feedforward to be essential for decoding transient signals, thereby complementing proposed design principles of temporal filtering, the ability to respond to sustained signals, but not to transient signals. More generally, we anticipate TopoDesign to help designing other synthetic circuits with non-intuitive dynamics, simply by assembling available biological components.


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