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https://www.readbyqxmd.com/read/28893975/agonist-dependent-and-independent-kappa-opioid-receptor-phosphorylation-showed-distinct-phosphorylation-patterns-and-resulted-in-different-cellular-outcomes
#1
Yi-Ting Chiu, Chongguang Chen, Daohai Yu, Stefan Schulz, Lee-Yuan Liu-Chen
We reported previously that the selective agonist U50,488H promoted phosphorylation of the mouse kappa opioid receptor (KOPR) at residues S356, T357, T363 and S369. Here, we found that agonist (U50,488H)-dependent KOPR phosphorylation at all the residues were mediated by Gi/oα proteins and multiple protein kinases [GRKs2, 3, 5 and 6 and protein kinase C (PKC)]. In addition, PKC activation by phorbol ester induced agonist-independent KOPR phosphorylation. Compared with U50,488H, PKC activation promoted much higher S356/T357 phosphorylation, much lower T363 phosphorylation and similar levels of S369 phosphorylation...
September 11, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28808053/navigating-the-conformational-landscape-of-g-protein-coupled-receptor-kinases-during-allosteric-activation
#2
Xin-Qiu Yao, M Claire Cato, Emily Labudde, Tyler S Beyett, John J G Tesmer, Barry J Grant
G protein-coupled receptors (GPCRs) are essential for transferring extracellular signals into carefully choreographed intracellular responses controlling diverse aspects of cell physiology. The duration of GPCR mediated signaling is primarily regulated via GPCR kinase (GRK)-mediated phosphorylation of activated receptors. Although many GRK structures have been reported, the mechanisms underlying GRK activation are not well understood, in part because it is unknown how these structures map to the conformational landscape available to this enzyme family...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28711719/g-protein-coupled-receptor-kinases-past-present-and-future
#3
REVIEW
Konstantin E Komolov, Jeffrey L Benovic
This review is provided in recognition of the extensive contributions of Dr. Robert J. Lefkowitz to the G protein-coupled receptor (GPCR) field and to celebrate his 75th birthday. Since one of the authors trained with Bob in the 80s, we provide a history of work done in the Lefkowitz lab during the 80s that focused on dissecting the mechanisms that regulate GPCR signaling, with a particular emphasis on the GPCR kinases (GRKs). In addition, we highlight structure/function characteristics of GRK interaction with GPCRs as well as a review of two recent reports that provide a molecular model for GRK-GPCR interaction...
July 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28711716/impact-of-paroxetine-on-proximal-%C3%AE-adrenergic-receptor-signaling
#4
Shuchi Guo, Rhonda L Carter, Laurel A Grisanti, Walter J Koch, Douglas G Tilley
β-adrenergic receptors (βAR) regulate numerous functions throughout the body, however G protein-coupled receptor kinase (GRK)-dependent desensitization of βAR has long been recognized as a maladaptive process in the progression of various disease states. Thus, the development of small molecule inhibitors of GRKs for the study of these processes and as potential therapeutics has been at the forefront of recent research efforts. Via structural and biochemical analyses, the selective serotonin reuptake inhibitor (SSRI) paroxetine was identified as a GRK2 inhibitor that enhances βAR-dependent cardiomyocyte and cardiac contractility and reverses cardiac dysfunction and myocardial βAR expression in mouse models of heart failure...
July 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28710495/tracing-the-vedic-saraswati-river-in-the-great-rann-of-kachchh
#5
Nitesh Khonde, Sunil Kumar Singh, D M Maurya, Vinai K Rai, L S Chamyal, Liviu Giosan
The lost Saraswati River mentioned in the ancient Indian tradition is postulated to have flown independently of the Indus River into the Arabian Sea, perhaps along courses of now defunct rivers such as Ghaggar, Hakra and Nara. The persistence of such a river during the Harappan Bronze Age and the Iron Age Vedic period is strongly debated. We drilled in the Great Rann of Kachchh (Kutch), an infilled gulf of the Arabian Sea, which must have received input from the Saraswati, if active. Nd and Sr isotopic measurements suggest that a distinct source may have been present before 10 ka...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28672188/effective-feather-degradation-and-keratinase-production-by-bacillus-pumilus-grk-for-its-application-as-bio-detergent-additive
#6
M Ramakrishna Reddy, K Sathi Reddy, Y Ranjita Chouhan, Hameeda Bee, Gopal Reddy
An effecient feather-degrading bacterium was isolated from poultry dumping yard and identified as Bacillus pumilus GRK based on 16S rRNA sequencing. Complete feather degradation (98.3±1.52%) with high keratinase production (373±4 U/ml) was observed in 24h under optimized conditions (substrate 1% (w/w); inoculum size 4% (v/v); pH 10; 200rpm at 37°C) with feathers as sole carbon and nitrogen source in tap water. The fermented broth was enriched with amino acids like tryptophan (221.44µg/ml), isoleucine (15...
June 15, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28591657/agc-kinases-mechanisms-of-regulation-%C3%A2-and-innovative-drug-development
#7
REVIEW
Alejandro E Leroux, Jörg O Schulze, Ricardo M Biondi
The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signalling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation...
June 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28572156/g-protein-coupled-receptor-kinase-2-is-a-critical-regulator-of-tnf%C3%AE-signaling-in-colon-epithelial-cells
#8
Michael D Steury, Peter C Lucas, Laura R McCabe, Narayanan Parameswaran
G-protein-coupled receptor kinase-2 (GRK2) belongs to the GRK family of serine/threonine protein kinases critical in the regulation of G-protein-coupled receptors. Apart from this canonical role, GRK2 is also involved in several signaling pathways via distinct intracellular interactomes. In the present study, we examined the role of GRK2 in TNFα signaling in colon epithelial cell-biological processes including wound healing, proliferation, apoptosis, and gene expression. Knockdown of GRK2 in the SW480 human colonic cells significantly enhanced TNFα-induced epithelial cell wound healing without any effect on apoptosis/proliferation...
June 27, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28524165/molecular-assembly-of-rhodopsin-with-g-protein-coupled-receptor-kinases
#9
Yuanzheng He, Xiang Gao, Devrishi Goswami, Li Hou, Kuntal Pal, Yanting Yin, Gongpu Zhao, Oliver P Ernst, Patrick Griffin, Karsten Melcher, H Eric Xu
G protein-coupled receptor kinases (GRKs) play pivotal roles in desensitizing GPCR signaling but little is known about how GRKs recognize and phosphorylate GPCRs due to the technical difficulties in detecting the highly dynamic GPCR/GRK interaction. By combining a genetic approach with multiple biochemical assays, we identified the key determinants for the assembly of the prototypical GPCR rhodopsin with its kinase GRK1. Our work reveals that the regulatory G-protein signaling homology (RH) domain of GRKs is the primary binding site to GPCRs and an active conformation of the GRK1 kinase domain is required for efficient interaction with rhodopsin...
June 2017: Cell Research
https://www.readbyqxmd.com/read/28512628/dysplasia-of-granulocytes-in-a-patient-with-hpv-disease-recurrent-infections-and-b-lymphopenia-a-novel-variant-of-whim-syndrome
#10
Giusella M F Moscato, Erica Giacobbi, Lucia Anemona, Silvia Di Cesare, Gigliola Di Matteo, Massimo Andreoni, Alessandro Mauriello, Viviana Moschese
WHIM syndrome is a condition in which affected persons have chronic peripheral neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus infection, and myelokathexis. Myelokathexis refers to the retention of mature neutrophils in the bone marrow (BM), which accounts for degenerative changes and hypersegmentation. Most patients present heterozygous autosomal dominant mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4 signaling impairs the receptor downregulation causing hyperactivation (gain-of-function) that affects BM homing for myelopoiesis and lymphopoiesis and the release of neutrophils in the bloodstream...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28483024/preliminary-analysis-of-parkinson-like-motor-coordination-abnormityin-brain-specific-hs100b-transgenic-mice
#11
Jialin Liu, Fang Zheng, Yan Long, Liu Tong, Yuan Zheng, Xiaoqing Liu, Chuan Qin
Objective To investigate the role of S100B in the development of Parkinson's disease (PD) and explore the possibility of brain-specific S100B transgenic mice as PD animal model. Methods The hS100B transgenic mice were established. The mice were divided into S100B transgenic group (TG),S100B knockout group (KG),and the non-transgenic control group (CG). Motor coordination ability of mice was measured by the rota-rod and pole-climbing test. The expressions of S100B,dopamine D1 receptor,dopamine D2 receptor,G protein-coupled receptor kinase (GRK)2,GRK5,and tyrosine hydroxylase in brain tissue were detected by reverse transcription-polymerase chain reaction and Western blot...
April 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28473253/g-protein-coupled-receptor-kinases-grks-in-tumorigenesis-and-cancer-progression-gpcr-regulators-and-signaling-hubs
#12
REVIEW
Laura Nogués, Julia Palacios-García, Clara Reglero, Verónica Rivas, María Neves, Catalina Ribas, Petronila Penela, Federico Mayor
Increasing evidences point to G protein-coupled receptor kinases (GRKs), a subfamily of protein kinase A/G/C-like kinases, as relevant players in cancer progression, in a cell-type and tumor-specific way. Alterations in the expression and/or activity of particular GRKs have been identified in several types of tumors, and demonstrated to modulate the proliferation, survival or invasive properties of tumor cells by acting as integrating signaling nodes. GRKs are able to regulate the functionality of both G protein-coupled receptors (GPCR) and growth factor receptors and to directly control cytosolic, cytoskeletal or nuclear signaling components of pathways relevant for these processes...
May 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28449947/barcoding-of-gpcr-trafficking-and-signaling-through-the-various-trafficking-roadmaps-by-compartmentalized-signaling-networks
#13
REVIEW
Suleiman W Bahouth, Mohammed M Nooh
Proper signaling by G protein coupled receptors (GPCR) is dependent on the specific repertoire of transducing, enzymatic and regulatory kinases and phosphatases that shape its signaling output. Activation and signaling of the GPCR through its cognate G protein is impacted by G protein-coupled receptor kinase (GRK)-imprinted "barcodes" that recruit β-arrestins to regulate subsequent desensitization, biased signaling and endocytosis of the GPCR. The outcome of agonist-internalized GPCR in endosomes is also regulated by sequence motifs or "barcodes" within the GPCR that mediate its recycling to the plasma membrane or retention and eventual degradation as well as its subsequent signaling in endosomes...
August 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28431242/structural-and-functional-analysis-of-a-%C3%AE-2-adrenergic-receptor-complex-with-grk5
#14
Konstantin E Komolov, Yang Du, Nguyen Minh Duc, Robin M Betz, João P G L M Rodrigues, Ryan D Leib, Dhabaleswar Patra, Georgios Skiniotis, Christopher M Adams, Ron O Dror, Ka Young Chung, Brian K Kobilka, Jeffrey L Benovic
The phosphorylation of agonist-occupied G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) functions to turn off G-protein signaling and turn on arrestin-mediated signaling. While a structural understanding of GPCR/G-protein and GPCR/arrestin complexes has emerged in recent years, the molecular architecture of a GPCR/GRK complex remains poorly defined. We used a comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange mass spectrometry (MS), electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β2-adrenergic receptor (β2AR)...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28379541/resistance-to-apoptosis-and-autophagy-leads-to-enhanced-survival-in-sertoli-cells
#15
Ferial Aslani, Tim Sebastian, Miguel Keidel, Suada Fröhlich, Hans-Peter Elsässer, Hans-Christian Schuppe, Jörg Klug, Poornima Mahavadi, Monika Fijak, Martin Bergmann, Andreas Meinhardt, Sudhanshu Bhushan
STUDY QUESTION: What is the underlying mechanism of Sertoli cell (SC) resistance to cell death? SUMMARY ANSWER: High expression of prosurvival B-cell lymphoma-2 (BCL2) proteins and inhibition of apoptosis and autophagy prolongs SC survival upon exposure to stress stimuli. WHAT IS KNOWN ALREADY: In human and in experimental models of orchitis, tolerogenic SC survive stress conditions, while germ cells undergo massive apoptosis. In general, non-dividing highly differentiated cells tend to resist stress conditions for a longer time by favoring activation of prosurvival mechanisms and inhibition of cell death pathways...
June 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28334166/grk5-regulates-social-behavior-via-suppression-of-mtorc1-signaling-in-medial-prefrontal-cortex
#16
Bing Niu, Peipei Liu, Minjie Shen, Cao Liu, Li Wang, Feifei Wang, Lan Ma
Impairments in social behaviors are features of a number of psychiatric diseases associated with subtle alterations in the medial prefrontal cortex (mPFC) circuitry. G protein-coupled receptor kinase (GRK) 5 is widely expressing in the cortex, however, its role in regulation of the mPFC activity and the development of social behaviors and psychiatric disorders is unclear. Here, we found that GRK5 dificiency in mice caused social behavior impairments. Further morphological, electrophysiological, and biochemical analyses showed abnormal postsynaptic ultrastructure, impaired excitatory synaptic transmission, the increased association of raptor with mTOR, and overactivated mTORC1-S6K signaling in the mPFC of Grk5-/- mice...
February 27, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28328746/cross-talk-between-insulin-signaling-and-g-protein-coupled-receptors
#17
Qin Fu, Qian Shi, Toni M West, Yang K Xiang
Diabetes is a major risk factor for the development of heart failure. One of the hallmarks of diabetes is insulin resistance associated with hyperinsulinemia. The literature shows that insulin and adrenergic signaling is intimately linked to each other; however, whether and how insulin may modulate cardiac adrenergic signaling and cardiac function remains unknown. Notably, recent studies have revealed that insulin receptor and β2 adrenergic receptor (β2AR) forms a membrane complex in animal hearts, bringing together the direct contact between 2 receptor signaling systems, and forming an integrated and dynamic network...
August 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28328744/noncanonical-roles-of-g-protein-coupled-receptor-kinases-in-cardiovascular-signaling
#18
Sarah M Schumacher, Walter J Koch
G protein-coupled receptor kinases (GRKs) are classically known for their role in regulating the activity of the largest known class of membrane receptors, which influence diverse biological processes in every cell type in the human body. As researchers have tried to uncover how this family of kinases, containing only 7 members, achieves selective and coordinated control of receptors, they have uncovered a growing number of noncanonical activities for these kinases. These activities include phosphorylation of nonreceptor targets and kinase-independent molecular interactions...
September 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28227032/a-statistical-model-for-stroke-outcome-prediction-and-treatment-planning
#19
Abhishek Sengupta, Vaibhav Rajan, Sakyajit Bhattacharya, G R K Sarma, Abhishek Sengupta, Vaibhav Rajan, Sakyajit Bhattacharya, G R K Sarma, Abhishek Sengupta, Grk Sarma, Vaibhav Rajan, Sakyajit Bhattacharya
Stroke is a major cause of mortality and long-term disability in the world. Predictive outcome models in stroke are valuable for personalized treatment, rehabilitation planning and in controlled clinical trials. We design a new multi-class classification model to predict outcome in the short-term, the putative therapeutic window for several treatments. Our model addresses the challenges of class imbalance, where the training data is dominated by samples of a single class, and highly correlated predictor and outcome variables, which makes learning the effects of treatments on the outcome difficult...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28214967/increased-atrial-%C3%AE-adrenergic-receptors-and-grk-2-gene-expression-can-play-a-fundamental-role-in-heart-failure-after-repair-of-congenital-heart-disease-with-cardiopulmonary-bypass
#20
Marcela Silva Oliveira, Fabio Carmona, Walter V A Vicente, Paulo H Manso, Karina M Mata, Mara Rúbia Celes, Erica C Campos, Simone G Ramos
Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction...
April 2017: Pediatric Cardiology
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