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https://www.readbyqxmd.com/read/27926858/g-protein-coupled-receptor-2-interacting-protein-1-controls-stalk-cell-fate-by-inhibiting-delta-like-4-notch1-signaling
#1
Syamantak Majumder, GuoFu Zhu, Xiangbin Xu, Sharon Senchanthisai, Dongyang Jiang, Hao Liu, Chao Xue, Xiaoqun Wang, Heidi Coia, Zhaoqiang Cui, Elaine M Smolock, Richard T Libby, Bradford C Berk, Jinjiang Pang
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926831/ras-association-domain-dimers-bring-proteins-together
#2
Holger Rehmann, Johannes L Bos
In this issue of Structure, Gingras et al. (2016) show that Ras association (RA) domains of the Rap1 and Ras interacting protein Rasip1 can form a dimer in the presence and absence of the small G protein Rap1. This provides an explanation for the observed complex formation in Rap1-mediated signaling.
December 6, 2016: Structure
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#3
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#4
Christine Oswald, Mathieu Rappas, James Kean, Andrew S Doré, James C Errey, Kirstie Bennett, Francesca Deflorian, John A Christopher, Ali Jazayeri, Jonathan S Mason, Miles Congreve, Robert M Cooke, Fiona H Marshall
Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells. They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases. Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27925669/biochemical-biophysical-and-cellular-techniques-to-study-the-guanine-nucleotide-exchange-factor-giv-girdin
#5
Pradipta Ghosh, Nicolas Aznar, Lee Swanson, I-Chung Lo, Inmaculada Lopez-Sanchez, Jason Ear, Cristina Rohena, Nicholas Kalogriopoulos, Linda Joosen, Ying Dunkel, Nina Sun, Peter Nguyen, Deepali Bhandari
Canonical signal transduction via heterotrimeric G proteins is spatiotemporally restricted, i.e., triggered exclusively at the plasma membrane, only by agonist activation of G protein-coupled receptors via a finite process that is terminated within a few hundred milliseconds. Recently, a rapidly emerging paradigm has revealed a noncanonical pathway for activation of heterotrimeric G proteins via the nonreceptor guanidine-nucleotide exchange factor, GIV/Girdin. Biochemical, biophysical, and functional studies evaluating this pathway have unraveled its unique properties and distinctive spatiotemporal features...
December 7, 2016: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/27925416/association-of-a-gain-of-function-variant-in-lgr4-with-central-obesity
#6
Yaoyu Zou, Tinglu Ning, Juan Shi, Maopei Chen, Lin Ding, Ya Huang, Sophie Kauderer, Min Xu, Bin Cui, Yufang Bi, Simin Liu, Jie Hong, Ruixin Liu, Guang Ning, Jiqiu Wang
OBJECTIVE: To determine the relationship of the gain-of-function variant A750T in leucine-rich repeat containing G protein-coupled receptor 4 (LGR4) with central obesity and related metabolic phenotypes. METHODS: The LGR4 A750T (c.2248 G > A) variant was detected by Sanger sequencing in a discovery young population and a validation community-based population with obesity from eastern China. Fat indices determined by anthropometry and computed tomography scans and clinical biochemical measurements were collected for association analysis...
December 7, 2016: Obesity
https://www.readbyqxmd.com/read/27924846/structure-and-dynamics-of-a-constitutively-active-neurotensin-receptor
#7
Brian E Krumm, Sangbae Lee, Supriyo Bhattacharya, Istvan Botos, Courtney F White, Haijuan Du, Nagarajan Vaidehi, Reinhard Grisshammer
Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound neurotensin receptor (NTSR1) and molecular dynamics simulations of agonist-occupied and ligand-free receptor. Comparison with the structure of a NTSR1 variant that has little constitutive activity reveals uncoupling of the ligand-binding domain from conserved connector residues, that effect conformational changes during GPCR activation...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924567/the-nuclear-translocation-of-erk
#8
Denise A Berti, Rony Seger
The ERK1 and ERK2 (ERK1/2) cascade is a central signaling pathway activated by a wide variety of extracellular agents that transmit the messages of G Protein Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs). Being such a central pathway, the activity of the cascade is well regulated, including by dynamic changes of the subcellular localization of components of the ERK1/2 cascade. In resting cells, ERK1/2 are localized in the cytosol due to their interactions with different anchoring proteins. After stimulation, ERK1/2 are phosphorylated by MEK1/2 on their regulatory TEY motif, which permits their detachment from the anchoring proteins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924341/structure-activity-relationship-of-novel-macrocyclic-biased-apelin-receptor-agonists
#9
Alexandre Murza, Xavier Sainsily, Jérôme Côté, Laurent Bruneau-Cossette, Élie Besserer-Offroy, Jean-Michel Longpré, Richard Leduc, Robert Dumaine, Olivier Lesur, Mannix Auger-Messier, Philippe Sarret, Éric Marsault
Apelin is the endogenous ligand for the G protein-coupled receptor APJ and exerts a key role in regulating cardiovascular functions. We report herein a novel series of macrocyclic analogues of apelin-13 in which the N- and C-terminal residues as well as the macrocycle composition were chemically modified to modulate structure-activity relationships on the APJ receptor. To this end, the binding affinity and the ability to engage G protein-dependent and G protein-independent signalling pathways of the resulting analogues were assessed...
December 7, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27924271/amino-acid-residues-of-bitter-taste-receptor-tas2r16-that-determine-sensitivity-in-primates-to-%C3%AE-glycosides
#10
Hiroo Imai, Nami Suzuki-Hashido, Yoshiro Ishimaru, Takanobu Sakurai, Lijie Yin, Wenshi Pan, Masaji Ishiguro, Katsuyoshi Masuda, Keiko Abe, Takumi Misaka, Hirohisa Hirai
In mammals, bitter taste is mediated by TAS2Rs, which belong to the family of seven transmembrane G protein-coupled receptors. Since TAS2Rs are directly involved in the interaction between mammals and their dietary sources, it is likely that these genes evolved to reflect species-specific diets during mammalian evolution. Here, we analyzed the amino acids responsible for the difference in sensitivities of TAS2R16s of various primates using a cultured cell expression system. We found that the sensitivity of TAS2R16 varied due to several amino acid residues...
2016: Biophysics and Physicobiology
https://www.readbyqxmd.com/read/27923934/gpcrdb-an-information-system-for-g-protein-coupled-receptors
#11
Vignir Isberg, Stefan Mordalski, Christian Munk, Krzysztof Rataj, Kasper Harpsøe, Alexander S Hauser, Bas Vroling, Andrzej J Bojarski, Gert Vriend, David E Gloriam
No abstract text is available yet for this article.
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923735/a-shadow-detector-for-photosynthesis-efficiency
#12
Kang-Ling Liao, Roger D Jones, Patrick McCarter, Meral Tunc-Ozdemir, James A Draper, Timothy C Elston, David Kramer, Alan M Jones
Plants tolerate large variations in the intensity of the light environment by controlling the efficiency of solar to chemical energy conversion. To do this, plants have a mechanism to detect the intensity, duration, and change in light as they experience moving shadows, flickering light, and cloud cover. Sugars are the primary products of CO2 fixation, a metabolic pathway that is rate limited by this solar energy conversion. We propose that sugar is a signal encoding information about the intensity, duration and change in the light environment...
December 3, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/27923683/role-of-a-tachykinin-related-peptide-and-its-receptor-in-modulating-the-olfactory-sensitivity-in-the-oriental-fruit-fly-bactrocera-dorsalis-hendel
#13
Shun-Hua Gui, Hong-Bo Jiang, Li Xu, Yu-Xia Pei, Xiao-Qiang Liu, Guy Smagghe, Jin-Jun Wang
Insect tachykinin-related peptide (TRP), an ortholog of tachykinin in vertebrates, has been linked with regulation of diverse physiological processes, such as olfactory perception, locomotion, aggression, lipid metabolism and myotropic activity. In this study, we investigated the function of TRP (BdTRP) and its receptor (BdTRPR) in an important agricultural pest, the oriental fruit fly Bactrocera dorsalis. BdTRPR is a typical G-protein coupled-receptor (GPCR), and it could be activated by the putative BdTRP mature peptides with the effective concentrations (EC50) at the nanomolar range when expressed in Chinese hamster ovary cells...
December 3, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27922938/skeletal-muscle-mass-is-associated-with-higher-dietary-protein-intake-and-lower-body-fat-in-postmenopausal-women-a-cross-sectional-study
#14
Thaís R Silva, Poli M Spritzer
OBJECTIVE: We investigated the association between skeletal muscle mass and dietary protein intake, habitual physical activity, body composition, and metabolic variables. METHODS: One hundred three healthy postmenopausal women from southern Brazil (age 55.2 ± 4.9 y, body mass index 27.2 ± 4.6 kg/m) were enrolled. Bone mineral density, %body fat, %trunk fat mass, and appendicular lean mass were assessed by dual-energy x-ray absorptiometry, resting metabolic rate by indirect calorimetry, and habitual physical activity by pedometer...
December 5, 2016: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/27922695/effects-of-five-candidate-laxatives-derived-from-liriope-platyphylla-on-the-5-ht-receptor-signaling-pathway-in-three-cell-types-present-in-the-transverse-colon
#15
Ji Eun Kim, Eun Kyoung Koh, Sung Hwa Song, Ji Eun Sung, Hyun Ah Lee, Hong Gu Lee, Young Whan Choi, Dae Youn Hwang
The laxative effects of aqueous extract of Liriope platyphylla (AEtLP) on loperamide (Lop)‑induced constipation have been reported; however, the key compounds and the mechanism underlying these effects remain unclear. Therefore, the laxative effects of five candidates derived from L. platyphylla: Diosgenin (DG), 5-hydroxymethylfurfural (5-HMF), adenosine (AD), hydroxypropyl cellulose (HPC) and uridine (UD) were investigated by examining the alteration of G protein α (Gα) expression, protein kinase C (PKC) phosphorylation and inositol triphosphate (IP3) concentration levels in the 5-hydroxytryptamine (5‑HT; serotonin) receptor signaling pathway...
December 5, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27922692/mir-195-inhibits-the-proliferation-and-migration-of-chondrocytes-by-targeting-git1
#16
Yang-Lin Gu, Xiao-Xu Rong, Li-Ting Wen, Guo-Xing Zhu, Ming-Quan Qian
Previous studies have demonstrated that G-protein coupled receptor kinase interacting protein-1 (GIT1) and microRNAs (miRNAs) serve an important role in chondrocyte proliferation and migration. However, a limited number of studies conducted thus far have investigated the association between GIT1 and miRNAs. In the present study, putative miR‑195 binding sites in the GIT1 3'‑untranslated region were identified using common bioinformatic algorithms (miRanda, TargetScan, miRBase and miRWalk), and it was demonstrated that they may be involved in regulating GIT1 expression...
December 5, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27922213/quantitative-maldi-ms-binding-assays-an-alternative-to-radiolabeling
#17
Maxime Rossato, Guillaume Miralles, Céline M'Kadmi, Mathieu Maingot, Muriel Amblard, Bernard Mouillac, Didier Gagne, Jean Martinez, Gilles Subra, Christine Enjalbal, Sonia Cantel
Radiolabeling of ligands is still the gold standard in the study of high-affinity receptor-ligand interactions. In an effort toward safer and simpler alternatives to the use of radioisotopes, we developed a quantitative and highly sensitive matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) method that relies on the use of chemically tagged ligands designed to be specifically detectable when present as traces in complex biological mixtures such as cellular lysates. This innovative technology allows easy, sensitive detection and accurate quantification of analytes at the sub-nanomolar level...
December 6, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27920205/molecular-determinants-of-the-sensitivity-to-gq-11-phospholipase-c-dependent-gating-gd3-potentiation-and-ca2-permeability-in-the-transient-receptor-potential-canonical-type-5-trpc5-channel
#18
Xingjuan Chen, Wennan Li, Ashley M Riley, Mario Soliman, Saikat Chakraborty, Christopher W Stamatkin, Alexander G Obukhov
Transient Receptor Potential Canonical type 5 (TRPC5) is a Ca(2+) permeable cation channel that is highly expressed in the brain and is implicated in motor coordination, innate fear behavior, and seizure-genesis. The channel is activated by a signal downstream of the G-protein-coupled receptor (GPCR)-Gq/11-phospholipase C (PLC) pathway. In this study, we aimed to identify the molecular mechanisms involved in regulating TRPC5 activity. We report that R593, a residue located in the E4 loop near the TRPC5's extracellular Gd(3+)-binding site, is critical for conferring the sensitivity to GPCR-Gq/11-PLC-dependent gating on TRPC5...
December 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27919726/g-protein-coupled-receptor-interactions-with-cholesterol-deep-in-the-membrane
#19
Samuel Genheden, Jonathan W Essex, Anthony G Lee
G-protein coupled receptors (GPCRs) are located in membranes rich in cholesterol. The membrane spanning surfaces of GPCRs contain exposed backbone carbonyl groups and residue side chains potentially capable of forming hydrogen bonds to cholesterol molecules buried deep within the hydrophobic core of the lipid bilayer. Coarse-grained molecular dynamics (CGMD) simulations allow the observation of GPCRs in cholesterol-containing lipid bilayers for long times (50μs), sufficient to ensure equilibration of the system...
December 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27918106/cannabidiol-activates-neuronal-precursor-genes-in-human-gingival-mesenchymal-stromal-cells
#20
Thangavelu Soundara Rajan, Sabrina Giacoppo, Domenico Scionti, Francesca Diomede, Gianpaolo Grassi, Federica Pollastro, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
In the last years, mesenchymal stromal cells (MSCs) from oral tissues have received considerable interest in regenerative medicine since they can be obtained with minimal invasive procedure and exhibit immunomodulatory properties. This study was aimed to investigate whether in vitro pre-treatment of MSCs obtained from human gingiva (hGMSCs) with Cannabidiol (CBD), a cannabinoid component produced by the plant Cannabis sativa, may promote human gingiva derived MSCs to differentiate towards neuronal precursor cells...
December 5, 2016: Journal of Cellular Biochemistry
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