scholarly journals The LPA3 Receptor: Regulation and Activation of Signaling Pathways

2021 ◽  
Vol 22 (13) ◽  
pp. 6704
Author(s):  
Karina Helivier Solís ◽  
M. Teresa Romero-Ávila ◽  
Alejandro Guzmán-Silva ◽  
J. Adolfo García-Sáinz
Keyword(s):  
Signaling Pathways ◽  
Lysophosphatidic Acid ◽  
Cellular Localization ◽  
Receptor Internalization ◽  
Therapeutic Interventions ◽  
Receptor Regulation ◽  
Signal Pathways ◽  
Lpa Receptor ◽  
Health And Disease ◽  
Receptor Family

The lysophosphatidic acid 3 receptor (LPA3) participates in different physiological actions and in the pathogenesis of many diseases through the activation of different signal pathways. Knowledge of the regulation of the function of the LPA3 receptor is a crucial element for defining its roles in health and disease. This review describes what is known about the signaling pathways activated in terms of its various actions. Next, we review knowledge on the structure of the LPA3 receptor, the domains found, and the roles that the latter might play in ligand recognition, signaling, and cellular localization. Currently, there is some information on the action of LPA3 in different cells and whole organisms, but very little is known about the regulation of its function. Areas in which there is a gap in our knowledge are indicated in order to further stimulate experimental work on this receptor and on other members of the LPA receptor family. We are convinced that knowledge on how this receptor is activated, the signaling pathways employed and how the receptor internalization and desensitization are controlled will help design new therapeutic interventions for treating diseases in which the LPA3 receptor is implicated.

scholarly journals LPA4/GPR23 Is a Lysophosphatidic Acid (LPA) Receptor Utilizing Gs-, Gq/Gi-mediated Calcium Signaling and G12/13-mediated Rho Activation

2006 ◽  
Vol 282 (7) ◽  
pp. 4310-4317 ◽  
Author(s):  
Chang-Wook Lee ◽  
Richard Rivera ◽  
Adrienne E. Dubin ◽  
Jerold Chun
Keyword(s):  
G Protein ◽  
Lysophosphatidic Acid ◽  
Tissue Expression ◽  
Fiber Formation ◽  
Receptor Internalization ◽  
Pharmacological Intervention ◽  
Pcr Analysis ◽  
Lpa Receptor ◽  
Neurite Retraction ◽  
Cation Conductance

Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that signals through G protein-coupled receptors (GPCRs) to produce a range of biological responses. A recently reported fourth receptor, LPA4/GPR23, was notable for its low homology to the previously identified receptors LPA1–3 and for its ability to increase intracellular concentrations of cAMP and calcium. However, the signaling pathways leading to LPA4-mediated induction of cAMP and calcium levels have not been reported. Using epitope-tagged LPA4, pharmacological intervention, and G protein mini-genes, we provide independent confirmatory evidence that supports LPA4 as a fourth LPA receptor, including LPA concentration-dependent responses and specific membrane binding. Importantly, we further demonstrate new LPA-dependent activities of LPA4 that include the following: receptor internalization; G12/13- and Rho-mediated neurite retraction and stress fiber formation; Gq protein and pertussis toxin-sensitive calcium mobilization and activation of a nonselective cation conductance; and cAMP increases mediated by Gs. The receptor is broadly expressed in embryonic tissues, including brain, as determined by Northern blot and reverse transcription-PCR analysis. Adult tissues have increased expression in skin, heart, and to a lesser extent, thymus. These data confirm the identification and extend the functionality of LPA4 as an LPA receptor, bringing the number of independently verified LPA receptors to five, with both overlapping and distinct signaling properties and tissue expression.

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review

2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Chemotherapy Resistance ◽  
Wnt Signaling Pathway ◽  
Therapeutic Interventions ◽  
Beta Catenin ◽  
Clinical Prognosis ◽  
Invasion And Migration ◽  
And Migration

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.

Epigenetics, Nutrition, Disease and Drug Development

2019 ◽  
Vol 16 (4) ◽  
pp. 386-391 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Dna Methylation ◽  
Drug Discovery ◽  
Rna Interference ◽  
Nutritional Requirements ◽  
Signal Pathways ◽  
Disease Development ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Health And Disease ◽  
Novel Drug

Epigenetic mechanisms comprising of DNA methylation, histone modifications and gene silencing by RNA interference have been strongly linked to the development and progression of various diseases. These findings have triggered research on epigenetic functions and signal pathways as targets for novel drug discovery. Dietary intake has also presented significant influence on human health and disease development and nutritional modifications have proven important in prevention, but also the treatment of disease. Moreover, a strong link between nutrition and epigenetic changes has been established. Therefore, in attempts to develop novel safer and more efficacious drugs, both nutritional requirements and epigenetic mechanisms need to be addressed.

scholarly journals Adhesion GPCRs in Glioblastoma

2021 ◽  
Author(s):  
Gabriele Stephan ◽  
Niklas Ravn-Boess ◽  
Dimitris G Placantonakis
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
The Past ◽  
Novel Treatment ◽  
The Family ◽  
Health And Disease ◽  
Basic Biology ◽  
G Protein Coupled ◽  
Potential Use ◽  
Receptor Family

Abstract Members of the adhesion family of G protein-coupled receptors (GPCRs) have received attention for their roles in health and disease, including cancer. Over the past decade, several members of the family have been implicated in the pathogenesis of glioblastoma. Here, we discuss the basic biology of adhesion GPCRs and review in detail specific members of the receptor family with known functions in glioblastoma. Finally, we discuss the potential use of adhesion GPCRs as novel treatment targets in neuro-oncology.

scholarly journals Single-cell biology to decode the immune cellular composition of kidney inflammation

2021 ◽  
Author(s):  
Yu Zhao ◽  
Ulf Panzer ◽  
Stefan Bonn ◽  
Christian F. Krebs
Keyword(s):  
Single Cell ◽  
Cell Biology ◽  
Computational Analysis ◽  
Immune Cell ◽  
Therapeutic Interventions ◽  
Experimental Setup ◽  
Disease Etiology ◽  
Rna Profiling ◽  
Immune Mediated ◽  
Health And Disease

AbstractSingle-cell biology is transforming the ability of researchers to understand cellular signaling and identity across medical and biological disciplines. Especially for immune-mediated diseases, a single-cell look at immune cell subtypes, signaling, and activity might yield fundamental insights into the disease etiology, mechanisms, and potential therapeutic interventions. In this review, we highlight recent advances in the field of single-cell RNA profiling and their application to understand renal function in health and disease. With a focus on the immune system, in particular on T cells, we propose some key directions of understanding renal inflammation using single-cell approaches. We detail the benefits and shortcomings of the various technological approaches outlined and give advice on potential pitfalls and challenges in experimental setup and computational analysis. Finally, we conclude with a brief outlook into a promising future for single-cell technologies to elucidate kidney function.

scholarly journals The STING1 network regulates autophagy and cell death

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ruoxi Zhang ◽  
Rui Kang ◽  
Daolin Tang
Keyword(s):  
Cell Death ◽  
Mitotic Cell ◽  
Therapeutic Interventions ◽  
Type I Interferons ◽  
Microbial Pathogens ◽  
Type I ◽  
Autophagic Degradation ◽  
Health And Disease ◽  
Shed Light ◽  
Pro Inflammatory Cytokines

AbstractCell death and immune response are at the core of life. In past decades, the endoplasmic reticulum (ER) protein STING1 (also known as STING or TMEM173) was found to play a fundamental role in the production of type I interferons (IFNs) and pro-inflammatory cytokines in response to DNA derived from invading microbial pathogens or damaged hosts by activating multiple transcription factors. In addition to this well-known function in infection, inflammation, and immunity, emerging evidence suggests that the STING1-dependent signaling network is implicated in health and disease by regulating autophagic degradation or various cell death modalities (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, mitotic cell death, and immunogenic cell death [ICD]). Here, we outline the latest advances in our understanding of the regulating mechanisms and signaling pathways of STING1 in autophagy and cell death, which may shed light on new targets for therapeutic interventions.

p21ras and protein kinase C function in distinct and interdependent signaling pathways in C3H 10T1/2 fibroblasts

1993 ◽  
Vol 13 (3) ◽  
pp. 1471-1479
Author(s):  
A Krook ◽  
M J Rapoport ◽  
S Anderson ◽  
H Pross ◽  
Y C Zhou ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Tyrosine Kinases ◽  
Signal Pathways ◽  
Mrna Levels ◽  
Ras Gene ◽  
Kinase C ◽  
Tetradecanoyl Phorbol Acetate ◽  
Cellular Signal

Both p21ras and protein kinase C (PKC) are believed to function downstream of plasma membrane-associated tyrosine kinases in cellular signal transduction pathways. However, it has remained controversial whether they function in the same pathway and, if so, what their relative position and functional relationship in such a pathway are. We investigated the possibilities that p21ras and PKC function either upstream or downstream of each other in a common linear pathway or that they function independently in colinear signal pathways. Either decreased expression of endogenous normal ras in fibroblasts transfected with an inducible antisense ras construct or overexpression of a mutant ras gene reduced the capacity of the phorbol ester tetradecanoyl phorbol acetate to trigger expression of the tetradecanoyl phorbol acetate-responsive and ras-dependent reporter gene osteopontin (OPN). PKC depletion decreased basal OPN mRNA levels, and the overexpression of ras restored OPN expression to the level of non-PKC-depleted cells. We propose a model in which ras and PKC function in distinct and interdependent signaling pathways.

scholarly journals Unlabeled lysophosphatidic acid receptor binding in free solution as determined by a compensated interferometric reader

2020 ◽  
Vol 61 (8) ◽  
pp. 1244-1251 ◽  
Author(s):  
Manisha Ray ◽  
Kazufumi Nagai ◽  
Yasuyuki Kihara ◽  
Amanda Kussrow ◽  
Michael N. Kammer ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Lysophosphatidic Acid ◽  
Specific Binding ◽  
Test Case ◽  
Free Solution ◽  
Label Free ◽  
Adhesive Properties ◽  
Lpa Receptor ◽  
System A ◽  
G Protein Coupled

Native interactions between lysophospholipids (LPs) and their cognate LP receptors are difficult to measure because of lipophilicity and/or the adhesive properties of lipids, which contribute to high levels of nonspecific binding in cell membrane preparations. Here, we report development of a free-solution assay (FSA) where label-free LPs bind to their cognate G protein-coupled receptors (GPCRs), combined with a recently reported compensated interferometric reader (CIR) to quantify native binding interactions between receptors and ligands. As a test case, the binding parameters between lysophosphatidic acid (LPA) receptor 1 (LPA1; one of six cognate LPA GPCRs) and LPA were determined. FSA-CIR detected specific binding through the simultaneous real-time comparison of bound versus unbound species by measuring the change in the solution dipole moment produced by binding-induced conformational and/or hydration changes. FSA-CIR identified KD values for chemically distinct LPA species binding to human LPA1 and required only a few nanograms of protein: 1-oleoyl (18:1; KD = 2.08 ± 1.32 nM), 1-linoleoyl (18:2; KD = 2.83 ± 1.64 nM), 1-arachidonoyl (20:4; KD = 2.59 ± 0.481 nM), and 1-palmitoyl (16:0; KD = 1.69 ± 0.1 nM) LPA. These KD values compared favorably to those obtained using the previous generation back-scattering interferometry system, a chip-based technique with low-throughput and temperature sensitivity. In conclusion, FSA-CIR offers a new increased-throughput approach to assess quantitatively label-free lipid ligand-receptor binding, including nonactivating antagonist binding, under near-native conditions.

Sign in / Sign up

Export Citation Format

Share Document