Expression of G protein-coupled receptors and related proteins in HEK293, AtT20, BV2, and N18 cell lines as revealed by microarray analysis
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE25901 | GEO | 2011/02/01
SECONDARY ACCESSION(S): PRJNA135767
REPOSITORIES: GEO
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Project description:BackgroundG protein coupled receptors (GPCRs) are one of the most widely studied gene superfamilies. Thousands of GPCR research studies have utilized heterologous expression systems such as human embryonic kidney cells (HEK293). Though often treated as 'blank slates', these cell lines nevertheless endogenously express GPCRs and related signaling proteins. The outcome of a given GPCR study can be profoundly influenced by this largely unknown complement of receptors and/or signaling proteins. Little easily accessible information exists that describes the expression profiles of the GPCRs in cell lines. What is accessible is often limited in scope - of the hundreds of GPCRs and related proteins, one is unlikely to find information on expression of more than a dozen proteins in a given cell line. Microarray technology has allowed rapid analysis of mRNA levels of thousands of candidate genes, but though often publicly available, the results can be difficult to efficiently access or even to interpret.ResultsTo bridge this gap, we have used microarrays to measure the mRNA levels of a comprehensive profile of non-chemosensory GPCRs and over a hundred GPCR signaling related gene products in four cell lines frequently used for GPCR research: HEK293, AtT20, BV2, and N18.ConclusionsThis study provides researchers an easily accessible mRNA profile of the endogenous signaling repertoire that these four cell lines possess. This will assist in choosing the most appropriate cell line for studying GPCRs and related signaling proteins. It also provides a better understanding of the potential interactions between GPCRs and those signaling proteins.
| S-EPMC3024950 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE25886: Analysis of mRNA levels of GPCR and GPCR-related signaling proteins in 3 mouse cell lines: AtT20, BV2 and N18 GSE25894: Analysis of mRNA levels of GPCR and GPCR-related signaling proteins in the HEK293 cell line Refer to individual Series
2011-02-01 | E-GEOD-25901 | biostudies-arrayexpress
Project description:Measurements of mRNA levels for non-chemosensory GPCRs, G proteins and selected G protein targets.
2011-02-01 | GSE25886 | GEO
Project description:Measurements of mRNA levels for non-chemosensory GPCRs, G proteins and selected G protein targets. Three mouse cell lines (AtT20, BV2 and N18), 4 replicates each. Overall data set includes mRNA levels for ~24,000 genes.
2011-02-01 | E-GEOD-25886 | biostudies-arrayexpress
Project description:Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN) and subsequent DA depletion in the striatum. Microglia activation and nigral iron accumulation play important roles in the pathogenesis of PD. Activated microglia show increased iron deposits. However, the relationship between microglia activation and iron accumulation remains unclear. In the present study, we aimed to determine how iron levels affect interleukin-6 (IL-6) synthesis, and the effect of IL-6 on cellular iron metabolism in BV2 microglial cells.IL-6 mRNA was up-regulated after FAC treatment for 12 h in BV2 cells. Iron regulatory protein 1 (IRP1) and divalent metal transporter 1 (DMT1) were up-regulated and iron exporter ferroportin 1 (FPN1) was down-regulated in BV2 cells after 24 h of IL-6 treatment. Phosphorylated JNK increased significantly compared to the control after BV2 cells were treated with IL-6 for 1 h. Pretreatment with SP600125 attenuated the up-regulation of IRP1 and DMT1 and down-regulation of FPN1 (compared to IL-6-treated group). These results suggest that iron load could increase IL-6 mRNA expression in BV2 cells. Further, IL-6 likely up-regulates IRP1 and DMT1 expression and down-regulates FPN1 expression in BV2 microglial cells through JNK signaling pathways.
| S-EPMC5495437 | biostudies-literature
Project description:G protein-coupled receptors (GPCRs) function as receptors for various neurotransmitters, hormones, cytokines, and metabolites. GPCR ligands impart differing degrees of signaling in the G protein and arrestin pathways, in phenomena called biased signaling, and each ligand for a given GPCR has a characteristic level of ability to activate or deactivate its target, which is referred to as its efficacy. The ligand efficacies and biased signaling of GPCRs remarkably affect the therapeutic properties of the ligands. However, these features of GPCRs can only be partially understood from the crystallography data, although numerous GPCR structures have been solved. NMR analyses have revealed that GPCRs have multiple interconverting substates, exchanging on various timescales, and that the exchange rates are related to the ligand efficacies and biased signaling. In addition, NMR analyses of GPCRs in the lipid bilayer environment of rHDLs revealed that the exchange rates are modulated by the lipid bilayer environment, highlighting the importance of the function-related dynamics in the lipid bilayer. In this review, we will describe several solution NMR studies that have clarified the conformational dynamics related to the ligand efficacy and biased signaling of GPCRs.
| S-EPMC6557943 | biostudies-literature
Project description:The cooperative nature of protein substructure and internal motion is a critical aspect of their functional competence about which little is known experimentally. NMR relaxation is used here to monitor the effects of high pressure on fast internal motion in the protein ubiquitin. In contrast to the main chain, the motions of the methyl-bearing side chains have a large and variable pressure dependence. Within the core, this pressure sensitivity correlates with the magnitude of motion at ambient pressure. Spatial clustering of the dynamic response to applied hydrostatic pressure is also seen, indicating localized cooperativity of motion on the sub-nanosecond time scale and suggesting regions of variable compressibility. These and other features indicate that the native ensemble contains a significant fraction of members with characteristics ascribed to the recently postulated "dry molten globule". The accompanying variable side-chain conformational entropy helps complete our view of the thermodynamic architecture underlying protein stability, folding, and function.
| S-EPMC3415598 | biostudies-literature
Project description:Despite many years of dedicated efforts, high-resolution structural determination of membrane proteins lags far behind that of soluble proteins. Computational methods in general, and molecular dynamics (MD) simulations in particular, have represented important alternative resources over the years to advance understanding of membrane protein structure and function. However, it is only recently that much progress has been achieved owing to new high-resolution membrane protein structures, specialized parallel computer architectures, and efficient simulation algorithms. This has definitely been the case for G protein-coupled receptors (GPCRs), which have assumed a leading role in the area of structural biology with several new structures appearing in the literature during the past five years. We provide here a concise overview of recent developments in computational biophysics of membrane proteins, using GPCRs as an example to showcase important information that can be derived from modern MD simulations.
| S-EPMC3164745 | biostudies-literature
Project description:G protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins that modulate their biology and pharmacology. However, the extent of these interactions and the mechanisms of their effects are not well understood. For example, one class of GPCR-interacting proteins, receptor activity-modifying proteins (RAMPs), comprise three related and ubiquitously expressed single-transmembrane span proteins. The RAMP family was discovered more than two decades ago, and since then GPCR-RAMP interactions and their functional consequences on receptor trafficking and ligand selectivity have been documented for several secretin (class B) GPCRs, most notably the calcitonin receptor-like receptor. Recent bioinformatics and multiplexed experimental studies suggest that GPCR-RAMP interactions might be much more widespread than previously anticipated. Recently, cryo-electron microscopy has provided high-resolution structures of GPCR-RAMP-ligand complexes, and drugs have been developed that target GPCR-RAMP complexes. In this review, we provide a summary of recent advances in techniques that allow the discovery of GPCR-RAMP interactions and their functional consequences and highlight prospects for future advances. We also provide an up-to-date list of reported GPCR-RAMP interactions based on a review of the current literature. SIGNIFICANCE STATEMENT: Receptor activity-modifying proteins (RAMPs) have emerged as modulators of many aspects of G protein-coupled receptor (GPCR)biology and pharmacology. The application of new methodologies to study membrane protein-protein interactions suggests that RAMPs interact with many more GPCRs than had been previously known. These findings, especially when combined with structural studies of membrane protein complexes, have significant implications for advancing GPCR-targeted drug discovery and the understanding of GPCR pharmacology, biology, and regulation.
| S-EPMC9832379 | biostudies-literature
Project description:BackgroundSubstance P (SP) is linked to itch and inflammation through activation of receptors on mast cells and sensory neurons. There is increasing evidence that SP functions through Mas-related G protein-coupled receptors (Mrgprs) in addition to its conventional receptor, neurokinin-1.ObjectiveBecause Mrgprs mediate some aspects of inflammation that had been considered mediated by neurokinin-1 receptor (NK-1R), we sought to determine whether itch induced by SP can also be mediated by Mrgprs.MethodsGenetic and pharmacologic approaches were used to evaluate the contribution of Mrgprs to SP-induced scratching behavior and activation of cultured dorsal root ganglion neurons from mice.ResultsSP-induced scratching behavior and activation of cultured dorsal root ganglion neurons was dependent on Mrgprs rather than NK-1R.ConclusionWe deduce that SP activates MrgprA1 on sensory neurons rather than NK-1R to induce itch.
| S-EPMC5546940 | biostudies-literature