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G coupled protein receptors

D A Bangasser, H Dong, J Carroll, Z Plona, H Ding, L Rodriguez, C McKennan, J G Csernansky, S H Seeholzer, R J Valentino
Several neuropsychiatric and neurodegenerative disorders share stress as a risk factor and are more prevalent in women than in men. Corticotropin-releasing factor (CRF) orchestrates the stress response, and excessive CRF is thought to contribute to the pathophysiology of these diseases. We previously found that the CRF1 receptor (CRF1) is sex biased whereby coupling to its GTP-binding protein, Gs, is greater in females, whereas β-arrestin-2 coupling is greater in males. This study used a phosphoproteomic approach in CRF-overexpressing (CRF-OE) mice to test the proof of principle that when CRF is in excess, sex-biased CRF1 coupling translates into divergent cell signaling that is expressed as different brain phosphoprotein profiles...
October 18, 2016: Molecular Psychiatry
Eun-Kyung Kwon, Chan-Ki Min, Yuri Kim, Jae-Won Lee, Abdimadiyeva Aigerim, Sebastian Schmidt, Hyun-Jun Nam, Seong Kyu Han, Kuglae Kim, Jeong Seok Cha, Hoyoung Kim, Sanguk Kim, Hyun-Soo Cho, Myung-Sik Choi, Nam-Hyuk Cho
Members of the herpesviral family use multiple strategies to hijack infected host cells and exploit cellular signaling for their pathogenesis and latent infection. Among the most intriguing weapons in the arsenal of pathogenic herpesviruses are the constitutively active virally-encoded G protein-coupled receptors (vGPCRs). Even though vGPCRs contribute to viral pathogenesis such as immune evasion and proliferative disorders, the molecular details of how vGPCRs continuously activate cellular signaling are largely unknown...
October 14, 2016: Biochimica et Biophysica Acta
Chafiq Hamdouchi, Steven D Kahl, Anjana Patel Lewis, Guemalli R Cardona, Richard W Zink, Keyue Chen, Thomas E Eessalu, James V Ficorilli, Marialuisa C Marcelo, Keith A Otto, Kelly L Wilbur, Jayana P Lineswala, Jared L Piper, D Scott Coffey, Stephanie A Sweetana, Joseph V Haas, Dawn A Brooks, Edward J Pratt, Ruth M Belin, Mark A Deeg, Xiaosu Ma, Ellen A Cannady, Jason T Johnson, Nathan P Yumibe, Qi Chen, Pranab Maiti, Chahrzad Montrose-Rafizadeh, Yanyun Chen, Anne Reifel Miller
The G protein-coupled receptor 40 (GPR40) also known as Free Fatty Acid Receptor 1 (FFAR1) is highly expressed in pancreatic, islet cells and responds to endogenous fatty acids resulting in amplification of insulin secretion only in the presence of elevated glucose levels. Hypothesis driven structural modifications to endogenous FFAs, focused on breaking planarity and reducing lipophilicity, led to the identification of spiropiperidine and tetrahydroquinoline acid derivatives as GPR40 agonists with unique pharmacology, selectivity and pharmacokinetic properties...
October 17, 2016: Journal of Medicinal Chemistry
Yohei Manabe, Marie Yoshimura, Kazuma Sakamaki, Asuka Inoue, Aya Kakinoki, Satoshi Hokari, Mariko Sakanaka, Junken Aoki, Hiroyuki Miyachi, Kazuyuki Furuta, Satoshi Tanaka
Accumulating evidence suggests that activated mast cells are involved in contact hypersensitivity, although the precise mechanisms of their activation are still not completely understood. We investigated the potential of common experimental allergens to induce mast cell activation using murine bone marrow-derived cultured mast cells and rat peritoneal mast cells. Among these allergens, 1-chloro-2,4-dinitrobenzene and 1-fluoro-2,4-dinirobenzene (DNFB) were found to induce degranulation of rat peritoneal mast cells...
October 17, 2016: European Journal of Immunology
Jiali Li, Xueshan Xiao, Shiqiang Li, Xiaoyun Jia, Xiangming Guo, Qingjiong Zhang
It has been previously reported that mutations in retinal G protein coupled receptor (RGR) are associated with retinitis pigmentosa. The present study aims to systemically analyze the potential role of variants of RGR in retinal diseases. Variants in coding regions and splice sites of RGR were selected from a whole exome sequencing dataset of 820 probands with various forms of genetic ocular diseases. Potential variants of RGR were further confirmed by Sanger sequencing and analyzed in available family members...
October 13, 2016: Molecular Medicine Reports
Anna Ngo, Ann Koay, Christian Pecquet, Carmen C Diaconu, Yasmine Ould-Amer, Qiwei Huang, Congbao Kang, Anders Poulsen, May Ann Lee, David Jenkins, Andrew Shiau, Stefan N Constantinescu, Meng Ling Choo
BACKGROUND: Rather than a Janus Kinase 2 inhibitor (ruxolitinib), a specific thrombopoietin receptor (TpoR) inhibitor would be more specific for the treatment of myeloproliferative neoplasms due to TpoR mutations. OBJECTIVE: A cell-based phenotypic approach to identify specific TpoR inhibitors was implemented and a library of 505,483 small molecules was screened for inhibitory effects on cells transformed by TpoR mutants. RESULTS: Among the identified hits are two analogs of 3-(4-piperidinyl) indole...
October 10, 2016: Combinatorial Chemistry & High Throughput Screening
Chen Zhang, Cassandra L Miller, Rakshya Gorkhali, Juan Zou, Kenneth Huang, Edward M Brown, Jenny J Yang
Ca(2+)-sensing receptors (CaSRs) play a central role in regulating extracellular calcium concentration ([Ca(2+)]o) homeostasis and many (patho)physiological processes in multiple organs. This regulation is orchestrated by a cooperative response to extracellular stimuli such as small changes in Ca(2+), Mg(2+), amino acids, and other ligands. In addition, CaSR is a pleiotropic receptor regulating several intracellular signaling pathways, including calcium mobilization and intracellular calcium oscillation. Nearly 200 mutations and polymorphisms have been found in CaSR in relation to a variety of human disorders associated with abnormal Ca(2+) homeostasis...
2016: Frontiers in Physiology
Wonnam Kim, John J Wysolmerski
The calcium-sensing receptor (CaSR) is expressed in normal breast epithelial cells and in breast cancer cells. During lactation, activation of the CaSR in mammary epithelial cells increases calcium transport into milk and inhibits parathyroid hormone-related protein (PTHrP) secretion into milk and into the circulation. The ability to sense changes in extracellular calcium allows the lactating breast to actively participate in the regulation of systemic calcium and bone metabolism, and to coordinate calcium usage with calcium availability during milk production...
2016: Frontiers in Physiology
Laziyan Mahemuti, Qixuan Chen, Melanie C Coughlan, Min Zhang, Maria Florian, Ryan J Mailloux, Xu-Liang Cao, Kylie A Scoggan, William G Willmore, Xiaolei Jin
Bisphenol A (BPA) has been shown to exert biological effects through estrogen receptor (ER)-dependent and ER-independent mechanisms. Recent studies suggest that prenatal exposure to BPA may increase the risk of childhood asthma. To investigate the underlying mechanisms in the actions of BPA, human fetal lung fibroblasts (hFLFs) were exposed to varying doses of BPA in culture for 24hr. Effects of BPA on localization and uptake of BPA, cell viability, release of immune and developmental modulators, cellular localization and expression of ERα, ERβ and G-protein coupled estrogen receptor 30 (GPR30), and effects of ERs antagonists on BPA-induced changes in endothelin-1 (ET-1) release were examined...
October 2016: Journal of Environmental Sciences (China)
Jianwei Zhang, Qi Li, Shaojin Zhang, Quanquan Xu, Tianen Wang
Lgr4 (leucine-rich repeat domain containing G protein-coupled receptor 4) is implicated in the transcriptional regulation of multiple histone demethylases in the progression of diverse cancers, but there are few reports concerning the molecular mechanism by which Lgr4 regulates histone demethylase activation in prostate cancer (PCa) progression. As Jmjd2a is a histone demethylase, in the current study, we investigated the relationship between interaction Lgr4 with Jmjd 2a and Jmjd2a/androgen receptor (AR) signaling pathway in PCa progression...
October 12, 2016: Experimental Cell Research
Donato Iacovazzo, Márta Korbonits
X-linked acrogigantism (XLAG) is a recently identified condition of early-onset GH excess resulting from the germline or somatic duplication of the GPR101 gene on chromosome Xq26.3. Thirty patients have been formally reported so far. The disease affects mostly females, occurs usually sporadically, and is characterised by early onset and marked overgrowth. Most patients present with concomitant hyperprolactinaemia. Histopathology shows pituitary hyperplasia or pituitary adenoma with or without associated hyperplasia...
September 29, 2016: Growth Hormone & IGF Research
Pil Seok Chae, Kyung Ho Cho, Orquidea Ribeiro, Yang Du, Elena Tikhonova, Jonas Mortensen, Kelsey Markham, Parameswaran Hariharan, Claus Løland, Lan Guan, Brian Kobilka, Bernadette Byrne
Detergents serve as useful tools for membrane protein structural and functional studies. Their amphipathic nature allows detergents to associate with the hydrophobic regions of membrane proteins whilst maintaining the proteins in aqueous solution. However, widely used conventional detergents have major limitations and thus there are major efforts to develop novel agents with improved properties. We prepared mesitylene-cored glucoside amphiphiles (MGAs) with three alkyl chains and compared these agents with previously developed xylene-linked maltoside agents (XMAs) with two alkyl chains and a conventional detergent (DDM)...
October 15, 2016: Chemistry: a European Journal
Thomas H Charpentier, Gary L Waldo, Emily G Lowery-Gionta, Krzysztof Krajewski, Brian D Strahl, Thomas L Kash, T Kendall Harden, John Sondek
In contrast to G protein-coupled receptors for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gaq binds its two major classes of effectors, the PLC-b isozymes and RhoGEFs related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gaq within its canonical binding site, consisting of a groove formed between switch II and helix a3. This information was exploited to synthesize peptides that bound active Gaq in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gaq...
October 14, 2016: Journal of Biological Chemistry
Amanda J Kennedy, Peiran Yang, Cai Read, Rhoda E Kuc, Lucy Yang, Emily J A Taylor, Colin W Taylor, Janet J Maguire, Anthony P Davenport
BACKGROUND: Circulating levels of chemerin are significantly higher in hypertensive patients and positively correlate with blood pressure. Chemerin activates chemokine-like receptor 1 (CMKLR1 or ChemR23) and is proposed to activate the "orphan" G-protein-coupled receptor 1 (GPR1), which has been linked with hypertension. Our aim was to localize chemerin, CMKLR1, and GPR1 in the human vasculature and determine whether 1 or both of these receptors mediate vasoconstriction. METHODS AND RESULTS: Using immunohistochemistry and molecular biology in conduit arteries and veins and resistance vessels, we localized chemerin to endothelium, smooth muscle, and adventitia and found that CMKLR1 and GPR1 were widely expressed in smooth muscle...
October 14, 2016: Journal of the American Heart Association
Blythe D Shepard, Lydie Cheval, Zita Peterlin, Stuart Firestein, Hermann Koepsell, Alain Doucet, Jennifer L Pluznick
Olfactory receptors (ORs) are G protein-coupled receptors which serve important sensory functions beyond their role as odorant detectors in the olfactory epithelium. Here we describe a novel role for one of these ORs, Olfr1393, as a regulator of renal glucose handling. Olfr1393 is specifically expressed in the kidney proximal tubule, which is the site of renal glucose reabsorption. Olfr1393 knockout mice exhibit urinary glucose wasting and improved glucose tolerance, despite euglycemia and normal insulin levels...
October 14, 2016: Scientific Reports
Robert Cooke, Miles Congreve
No abstract text is available yet for this article.
October 14, 2016: Future Medicinal Chemistry
Youn Yi Jo, Ji Yeon Lee, Chul-Kyu Park
The neuropeptide substance P (SP) is expressed in primary sensory neurons and is commonly regarded as a "pain" neurotransmitter. Upon peripheral inflammation, SP activates the neurokinin-1 (NK-1) receptor and potentiates activity of transient receptor potential vanilloid subtype 1 (TRPV1), which is coexpressed by nociceptive neurons. Therefore, SP functions as an important neurotransmitter involved in the hypersensitization of inflammatory pain. Resolvin E1 (RvE1), derived from omega-3 polyunsaturated fatty acids, inhibits TRPV1 activity via activation of the chemerin 23 receptor (ChemR23)-an RvE1 receptor located in dorsal root ganglion neurons-and therefore exerts an inhibitory effect on inflammatory pain...
2016: Mediators of Inflammation
Nan Gao, Tao Liang, Yuan Yuan, Xiuchan Xiao, Yihuan Zhao, Yanzhi Guo, Menglong Li, Xuemei Pu
G-protein-coupled receptors (GPCRs) are important drug targets and generally activated by ligands. However, some experiments found that GPCRs also give rise to constitutive activity through some mutations (viz., CAM), which are usually associated with different kinds of diseases. However, the mechanisms of CAMs and their roles in interactions with drug-ligands are unclear in experiments. Herein, we used microsecond molecular dynamics simulations to study the effect of one important F282L mutation on β2AR in order to address the questions above...
October 13, 2016: Physical Chemistry Chemical Physics: PCCP
Nijiro Nohata, Yusuke Goto, J Silvio Gutkind
The G-protein-coupled receptor (GPCR) family is the largest family of cell-surface receptors involved in signal transduction. Aberrant expression of GPCRs and G proteins are frequently associated with prevalent human diseases, including cancer. In fact, GPCRs represent the therapeutic targets of more than a quarter of the clinical drugs currently on the market. MiRNAs (miRNAs) are also aberrantly expressed in many human cancers, and they have significant roles in the initiation, development and metastasis of human malignancies...
October 13, 2016: Journal of Human Genetics
Christoph Tondera, Markus Laube, Jens Pietzsch
The EF-hand type calcium-binding protein S100A12 exerts numerous intra- and extracellular functions of (patho)physiological relevance. Therefore, receptors of S100A12 are of high interest for research and clinical applications. Beside the extensively studied receptor for advanced glycation endproducts (RAGE), G-protein coupled receptors and more recently, scavenger receptors are suggested to be putative S100A12 receptors. Own findings and further information from the literature predestined CD36, a class B scavenger receptor, as promising candidate...
October 12, 2016: Amino Acids
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