scholarly journals Autotaxin: Its Role in Biology of Melanoma Cells and as a Pharmacological Target

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Maciej Jankowski
Keyword(s):  
Lysophosphatidic Acid ◽  
Main Product ◽  
Normal Development ◽  
Malignant Tumors ◽  
Biological Fluids ◽  
Immunological Response ◽  
Melanoma Cells ◽  
G Protein Coupled Receptors ◽  
The Impact ◽  
G Protein Coupled

Autotaxin (ATX) is an extracellular lysophospholipase D (lysoPLD) released from normal cells and cancer cells. Activity of ATX is detected in various biological fluids. The lysophosphatidic acid (LPA) is the main product of ATX. LPA acting through specific G protein-coupled receptors (LPA1-LPA6) affects immunological response, normal development, and malignant tumors' formation and progression. In this review, the impact of autotoxin on biology of melanoma cells and potential treatment is discussed.

scholarly journals US28: HCMV’s Swiss Army Knife

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 445 ◽  
Author(s):  
Benjamin Krishna ◽  
William Miller ◽  
Christine O’Connor
Keyword(s):  
Latent Infection ◽  
Viral Latency ◽  
Lytic Replication ◽  
G Protein Coupled Receptors ◽  
Disease States ◽  
Cellular Pathways ◽  
The Impact ◽  
Multiple Signaling ◽  
G Protein Coupled ◽  
Multifunctional Properties

US28 is one of four G protein coupled receptors (GPCRs) encoded by human cytomegalovirus (HCMV). The US28 protein (pUS28) is a potent signaling molecule that alters a variety of cellular pathways that ultimately alter the host cell environment. This viral GPCR is expressed not only in the context of lytic replication but also during viral latency, highlighting its multifunctional properties. pUS28 is a functional GPCR, and its manipulation of multiple signaling pathways likely impacts HCMV pathogenesis. Herein, we will discuss the impact of pUS28 on both lytic and latent infection, pUS28-mediated signaling and its downstream consequences, and the influence this viral GPCR may have on disease states, including cardiovascular disease and cancer. We will also discuss the potential for and progress towards exploiting pUS28 as a novel therapeutic to combat HCMV.

scholarly journals Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells

2016 ◽  
Vol 371 (1685) ◽  
pp. 20150040 ◽  
Author(s):  
Y. Wenger ◽  
W. Buzgariu ◽  
B. Galliot
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
G Protein Coupled Receptors ◽  
The Body ◽  
Neurogenic Genes ◽  
Cell Type Specific ◽  
The Impact ◽  
G Protein Coupled ◽  
Body Column ◽  
Compensatory Regulation

Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory–motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra , we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors ( Dlx , Dlx1 , DMBX1/Manacle , Ets1 , Gli3 , KLF11 , LMX1A , ZNF436 , Shox1 ), epitheliopeptides ( Arminins , PW peptide ), neurosignalling components ( CAMK1D , DDCl2 , Inx1 ), ligand-ion channel receptors ( CHRNA1 , NaC7 ), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.

Selective blockade of lysophosphatidic acid LPA3 receptors reduces murine renal ischemia-reperfusion injury

2003 ◽  
Vol 285 (3) ◽  
pp. F565-F574 ◽  
Author(s):  
Mark D. Okusa ◽  
Hong Ye ◽  
Liping Huang ◽  
Laura Sigismund ◽  
Timothy Macdonald ◽  
...  
Keyword(s):  
Lysophosphatidic Acid ◽  
Ischemia Reperfusion Injury ◽  
Rank Order ◽  
Ischemia Reperfusion ◽  
G Protein Coupled Receptors ◽  
Renal Ischemia ◽  
Outer Medulla ◽  
Selective Blockade ◽  
G Protein Coupled ◽  
Receptor Mrnas

Lysophosphatidic acid (LPA) released during ischemia has diverse physiological effects via its G protein-coupled receptors, LPA1, LPA2, and LPA3 (formerly Edg-2, -4, and -7). We tested the hypothesis that selective blockade of LPA receptors affords protection from renal ischemia-reperfusion (I/R) injury. By real-time PCR, LPA1-3 receptor mRNAs were expressed in mouse renal cortex, outer medulla, and inner medulla with the following rank order LPA3 = LPA2 > LPA1. In C57BL/6 mice whose kidneys were subjected to ischemia and reperfusion, treatment with a selective LPA3 agonist, oleoyl-methoxy phosphothionate (OMPT), enhanced injury. In contrast, a dual LPA1/LPA3-receptor antagonist, VPC-12249, reduced I/R injury, but this protective effect was lost when the antagonist was coadministered with OMPT. Interestingly, delaying administration of VPC-12249 until 30 min after the start of reperfusion did not alter its efficacy significantly. We conclude that VPC-12249 reduces renal I/R injury predominantly by LPA3 receptor blockade and could serve as a novel compound in the treatment of ischemia acute renal failure.

scholarly journals Autotaxin, a Secreted Lysophospholipase D, Is Essential for Blood Vessel Formation during Development

2006 ◽  
Vol 26 (13) ◽  
pp. 5015-5022 ◽  
Author(s):  
Laurens A. van Meeteren ◽  
Paula Ruurs ◽  
Catelijne Stortelers ◽  
Peter Bouwman ◽  
Marga A. van Rooijen ◽  
...  
Keyword(s):  
Lysophosphatidic Acid ◽  
Critical Role ◽  
G Protein Coupled Receptors ◽  
Blood Vessel Formation ◽  
Lysophospholipase D ◽  
Motility Factor ◽  
Nucleotide Pyrophosphatase ◽  
G Protein Coupled ◽  
Deficient Mice

ABSTRACT Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that promotes cell migration, metastasis, and angiogenesis. ATX generates lysophosphatidic acid (LPA), a lipid mitogen and motility factor that acts on several G protein-coupled receptors. Here we report that ATX-deficient mice die at embryonic day 9.5 (E9.5) with profound vascular defects in yolk sac and embryo resembling the Gα13 knockout phenotype. Furthermore, at E8.5, ATX-deficient embryos showed allantois malformation, neural tube defects, and asymmetric headfolds. The onset of these abnormalities coincided with increased expression of ATX and LPA receptors in normal embryos. ATX heterozygous mice appear healthy but show half-normal ATX activity and plasma LPA levels. Our results reveal a critical role for ATX in vascular development, indicate that ATX is the major LPA-producing enzyme in vivo, and suggest that the vascular defects in ATX-deficient embryos may be explained by loss of LPA signaling through Gα13.

scholarly journals Fungal G-Protein-Coupled Receptors: A Promising Mediator of the Impact of Extracellular Signals on Biosynthesis of Ochratoxin A

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Gao ◽  
Xinge Xu ◽  
Kunlun Huang ◽  
Zhihong Liang
Keyword(s):  
G Protein ◽  
Ochratoxin A ◽  
G Protein Coupled Receptors ◽  
Aspergillus Ochraceus ◽  
Transmembrane Receptors ◽  
Environmental Signals ◽  
Extracellular Signals ◽  
Fungal Biology ◽  
The Impact ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) are transmembrane receptors involved in transducing signals from the external environment inside the cell, which enables fungi to coordinate cell transport, metabolism, and growth to promote their survival, reproduction, and virulence. There are 14 classes of GPCRs in fungi involved in sensing various ligands. In this paper, the synthesis of mycotoxins that are GPCR-mediated is discussed with respect to ligands, environmental stimuli, and intra-/interspecific communication. Despite their apparent importance in fungal biology, very little is known about the role of ochratoxin A (OTA) biosynthesis by Aspergillus ochraceus and the ligands that are involved. Fortunately, increasing evidence shows that the GPCR that involves the AF/ST (sterigmatocystin) pathway in fungi belongs to the same genus. Therefore, we speculate that GPCRs play an important role in a variety of environmental signals and downstream pathways in OTA biosynthesis. The verification of this inference will result in a more controllable GPCR target for control of fungal contamination in the future.

scholarly journals Lysophosphatidic Acid and Hematopoiesis: From Microenvironmental Effects to Intracellular Signaling

2020 ◽  
Vol 21 (6) ◽  
pp. 2015 ◽  
Author(s):  
Kuan-Hung Lin ◽  
Jui-Chung Chiang ◽  
Ya-Hsuan Ho ◽  
Chao-Ling Yao ◽  
Hsinyu Lee
Keyword(s):  
Stem Cells ◽  
G Protein ◽  
Lysophosphatidic Acid ◽  
Intracellular Signaling ◽  
Lineage Tracing ◽  
G Protein Coupled Receptors ◽  
Hematopoietic Stem ◽  
Extracellular Microenvironment ◽  
G Protein Coupled ◽  
Prevention And Therapy

Vertebrate hematopoiesis is a complex physiological process that is tightly regulated by intracellular signaling and extracellular microenvironment. In recent decades, breakthroughs in lineage-tracing technologies and lipidomics have revealed the existence of numerous lipid molecules in hematopoietic microenvironment. Lysophosphatidic acid (LPA), a bioactive phospholipid molecule, is one of the identified lipids that participates in hematopoiesis. LPA exhibits various physiological functions through activation of G-protein-coupled receptors. The functions of these LPARs have been widely studied in stem cells, while the roles of LPARs in hematopoietic stem cells have rarely been examined. Nonetheless, mounting evidence supports the importance of the LPA-LPAR axis in hematopoiesis. In this article, we have reviewed regulation of hematopoiesis in general and focused on the microenvironmental and intracellular effects of the LPA in hematopoiesis. Discoveries in these areas may be beneficial to our understanding of blood-related disorders, especially in the context of prevention and therapy for anemia.

Glucagon counteracts interleukin-6-dependent gene expression by redundant action of Epac and PKA

2011 ◽  
Vol 392 (12) ◽  
pp. 1123-1134 ◽  
Author(s):  
Christina Khouri ◽  
Anna Dittrich ◽  
Sara Dutton Sackett ◽  
Bernd Denecke ◽  
Christian Trautwein ◽  
...  
Keyword(s):  
Gene Expression ◽  
G Protein ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Biological Response ◽  
Underlying Mechanism ◽  
G Protein Coupled Receptors ◽  
Counterregulatory Hormones ◽  
The Impact ◽  
G Protein Coupled

AbstractInflammation is the biological response to injurious stimuli. In the initial phase of the inflammatory process, interleukin-6 (IL-6) is the main inducer of acute phase protein expression in the liver. A prolonged acute phase response is characterised by a disturbed glucose homeostasis and elevated levels of IL-6, insulin, and counterregulatory hormones such as glucagon. Several studies deal with the impact of IL-6 on glucagon-dependent gene expression. In contrast, only very little is known about the influence of G-protein-coupled receptors on IL-6 signalling. Therefore, the aim of this study is to elucidate the regulation of IL-6-induced gene expression by glucagon. We could reveal a novel mechanism of negative regulation of IL-6-induced MAP kinase activation by glucagon in primary murine hepatocytes. IL-6-dependent induction of the ERK-dependent target geneTfpi2, coding for a Kunitz-type serine protease inhibitor, was strongly down-regulated by glucagon treatment. Studying the underlying mechanism revealed a redundant action of the signalling molecules exchange protein activated by cyclic AMP (Epac) and protein kinase A. The metabolic hormone glucagon interferes in IL-6-induced gene expression. This observation is indicative for a regulatory role of G-protein-coupled receptors in the IL-6-dependent inflammatory response.

scholarly journals Lysophospholipids in the limelight

2002 ◽  
Vol 158 (2) ◽  
pp. 197-199 ◽  
Author(s):  
Wouter H. Moolenaar
Keyword(s):  
Growth Factor ◽  
Cell Motility ◽  
Tumor Progression ◽  
G Protein ◽  
Lysophosphatidic Acid ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Serum Phospholipid ◽  
A Cell ◽  
G Protein Coupled

Lysophosphatidic acid (LPA) is a serum phospholipid that evokes growth factor–like responses in many cell types through the activation of its G protein–coupled receptors. Although much is known about LPA signaling, it has remained unclear where and how bioactive LPA is produced. Umezu-Goto et al. (2002)(this issue, page 227) have purified a serum lysophospholipase D that generates LPA from lysophosphatidylcholine and found it to be identical to autotaxin, a cell motility–stimulating ectophosphodiesterase implicated in tumor progression. This result is surprising, as there was previously no indication that autotaxin could act as a phospholipase.

scholarly journals Mycobacteria Manipulate G-Protein-Coupled Receptors to Increase Mucosal Rac1 Expression in the Lungs

2016 ◽  
Vol 9 (3) ◽  
pp. 318-329 ◽  
Author(s):  
Nader Alaridah ◽  
Nataliya Lutay ◽  
Erik Tenland ◽  
Anna Rönnholm ◽  
Oskar Hallgren ◽  
...  
Keyword(s):  
G Protein ◽  
Airway Epithelial Cells ◽  
G Protein Coupled Receptors ◽  
The Body ◽  
Airway Epithelial ◽  
Mucosal Vaccination ◽  
Mapk Signalling Pathway ◽  
The Impact ◽  
G Protein Coupled ◽  
Rac1 Expression

Mycobacterium bovis bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB). BCG mimics M. tuberculosis (Mtb) in its persistence in the body and is used as a benchmark to compare new vaccine candidates. BCG was originally designed for mucosal vaccination, but comprehensive knowledge about its interaction with epithelium is currently lacking. We used primary airway epithelial cells (AECs) and a murine model to investigate the initial events of mucosal BCG interactions. Furthermore, we analysed the impact of the G-protein-coupled receptors (GPCRs), CXCR1 and CXCR2, in this process, as these receptors were previously shown to be important during TB infection. BCG infection of AECs induced GPCR-dependent Rac1 up-regulation, resulting in actin redistribution. The altered distribution of the actin cytoskeleton involved the MAPK signalling pathway. Blocking of the CXCR1 or CXCR2 prior to infection decreased Rac1 expression, and increased epithelial transcriptional activity and epithelial cytokine production. BCG infection did not result in epithelial cell death as measured by p53 phosphorylation and annexin. This study demonstrated that BCG infection of AECs manipulated the GPCRs to suppress epithelial signalling pathways. Future vaccine strategies could thus be improved by targeting GPCRs.

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