Base de dados : MEDLINE
Pesquisa : D12.644.360.024.098 [Categoria DeCS]
Referências encontradas : 2063 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 207 ir para página                         

  1 / 2063 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28461104
[Au] Autor:Prokop S; Perry NA; Vishnivetskiy SA; Toth AD; Inoue A; Milligan G; Iverson TM; Hunyady L; Gurevich VV
[Ad] Endereço:Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
[Ti] Título:Differential manipulation of arrestin-3 binding to basal and agonist-activated G protein-coupled receptors.
[So] Source:Cell Signal;36:98-107, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Non-visual arrestins interact with hundreds of different G protein-coupled receptors (GPCRs). Here we show that by introducing mutations into elements that directly bind receptors, the specificity of arrestin-3 can be altered. Several mutations in the two parts of the central "crest" of the arrestin molecule, middle-loop and C-loop, enhanced or reduced arrestin-3 interactions with several GPCRs in receptor subtype and functional state-specific manner. For example, the Lys139Ile substitution in the middle-loop dramatically enhanced the binding to inactive M muscarinic receptor, so that agonist activation of the M did not further increase arrestin-3 binding. Thus, the Lys139Ile mutation made arrestin-3 essentially an activation-independent binding partner of M , whereas its interactions with other receptors, including the ß -adrenergic receptor and the D and D dopamine receptors, retained normal activation dependence. In contrast, the Ala248Val mutation enhanced agonist-induced arrestin-3 binding to the ß -adrenergic and D dopamine receptors, while reducing its interaction with the D dopamine receptor. These mutations represent the first example of altering arrestin specificity via enhancement of the arrestin-receptor interactions rather than selective reduction of the binding to certain subtypes.
[Mh] Termos MeSH primário: Arrestinas/metabolismo
Receptores Acoplados a Proteínas-G/agonistas
Receptores Acoplados a Proteínas-G/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Arrestinas/química
Células COS
Bovinos
Cercopithecus aethiops
Sequência Conservada
Células HEK293
Seres Humanos
Lisina/metabolismo
Proteínas Mutantes/metabolismo
Mutação/genética
Ligação Proteica
Estrutura Secundária de Proteína
Rodopsina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arrestins); 0 (Mutant Proteins); 0 (Receptors, G-Protein-Coupled); 0 (arrestin3); 9009-81-8 (Rhodopsin); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  2 / 2063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28795803
[Au] Autor:Schubert M; Stichel J; Du Y; Tough IR; Sliwoski G; Meiler J; Cox HM; Weaver CD; Beck-Sickinger AG
[Ad] Endereço:Faculty of Biosciences, Pharmacy and Psychology, Institute of Biochemistry, Leipzig University , Leipzig 04103, Germany.
[Ti] Título:Identification and Characterization of the First Selective Y Receptor Positive Allosteric Modulator.
[So] Source:J Med Chem;60(17):7605-7612, 2017 Sep 14.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human Y receptor (Y R) and its cognate ligand, pancreatic polypeptide (PP), are involved in the regulation of energy expenditure, satiety, and food intake. This system represents a potential target for the treatment of metabolic diseases and has been extensively investigated and validated in vivo. Here, we present the compound tBPC (tert-butylphenoxycyclohexanol), a novel and selective Y R positive allosteric modulator that potentiates Y R activation in G-protein signaling and arrestin3 recruitment experiments. The compound has no effect on the binding of the orthosteric ligands, implying its allosteric mode of action at the Y R and evidence for a purely efficacy-driven positive allosteric modulation. Finally, the ability of tBPC to selectively potentiate Y R agonism initiated by PP was confirmed in mouse descending colon mucosa preparations expressing native Y R, demonstrating Y R positive allosteric modulation in vitro.
[Mh] Termos MeSH primário: Regulação Alostérica/efeitos dos fármacos
Cicloexanóis/química
Cicloexanóis/farmacologia
Proteínas de Ligação ao GTP/metabolismo
Receptores de Neuropeptídeo Y/agonistas
Receptores de Neuropeptídeo Y/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Arrestinas/metabolismo
Células COS
Cercopithecus aethiops
Células HEK293
Seres Humanos
Modelos Moleculares
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arrestins); 0 (Cyclohexanols); 0 (Receptors, Neuropeptide Y); 0 (arrestin3); 0 (neuropeptide Y4 receptor); EC 3.6.1.- (GTP-Binding Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00976


  3 / 2063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28753425
[Au] Autor:Zhou XE; He Y; de Waal PW; Gao X; Kang Y; Van Eps N; Yin Y; Pal K; Goswami D; White TA; Barty A; Latorraca NR; Chapman HN; Hubbell WL; Dror RO; Stevens RC; Cherezov V; Gurevich VV; Griffin PR; Ernst OP; Melcher K; Xu HE
[Ad] Endereço:VARI-SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Laboratory of Structural Sciences, Center for Structural Biology and Drug Discovery, Van Andel Rese
[Ti] Título:Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors.
[So] Source:Cell;170(3):457-469.e13, 2017 Jul 27.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:G protein-coupled receptors (GPCRs) mediate diverse signaling in part through interaction with arrestins, whose binding promotes receptor internalization and signaling through G protein-independent pathways. High-affinity arrestin binding requires receptor phosphorylation, often at the receptor's C-terminal tail. Here, we report an X-ray free electron laser (XFEL) crystal structure of the rhodopsin-arrestin complex, in which the phosphorylated C terminus of rhodopsin forms an extended intermolecular ß sheet with the N-terminal ß strands of arrestin. Phosphorylation was detected at rhodopsin C-terminal tail residues T336 and S338. These two phospho-residues, together with E341, form an extensive network of electrostatic interactions with three positively charged pockets in arrestin in a mode that resembles binding of the phosphorylated vasopressin-2 receptor tail to ß-arrestin-1. Based on these observations, we derived and validated a set of phosphorylation codes that serve as a common mechanism for phosphorylation-dependent recruitment of arrestins by GPCRs.
[Mh] Termos MeSH primário: Arrestinas/química
Rodopsina/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Arrestinas/metabolismo
Cromatografia Líquida
Seres Humanos
Camundongos
Modelos Moleculares
Fosforilação
Ratos
Rodopsina/metabolismo
Alinhamento de Sequência
Espectrometria de Massas em Tandem
Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arrestins); 0 (arrestin 1 protein, mouse); 9009-81-8 (Rhodopsin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE


  4 / 2063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28683816
[Au] Autor:Indrischek H; Prohaska SJ; Gurevich VV; Gurevich EV; Stadler PF
[Ad] Endereço:Computational EvoDevo Group, Department of Computer Science, Universität Leipzig, Härtelstraße 16-18, Leipzig, D-04107, Germany. henrike@bioinf.uni-leipzig.de.
[Ti] Título:Uncovering missing pieces: duplication and deletion history of arrestins in deuterostomes.
[So] Source:BMC Evol Biol;17(1):163, 2017 Jul 06.
[Is] ISSN:1471-2148
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The cytosolic arrestin proteins mediate desensitization of activated G protein-coupled receptors (GPCRs) via competition with G proteins for the active phosphorylated receptors. Arrestins in active, including receptor-bound, conformation are also transducers of signaling. Therefore, this protein family is an attractive therapeutic target. The signaling outcome is believed to be a result of structural and sequence-dependent interactions of arrestins with GPCRs and other protein partners. Here we elucidated the detailed evolution of arrestins in deuterostomes. RESULTS: Identity and number of arrestin paralogs were determined searching deuterostome genomes and gene expression data. In contrast to standard gene prediction methods, our strategy first detects exons situated on different scaffolds and then solves the problem of assigning them to the correct gene. This increases both the completeness and the accuracy of the annotation in comparison to conventional database search strategies applied by the community. The employed strategy enabled us to map in detail the duplication- and deletion history of arrestin paralogs including tandem duplications, pseudogenizations and the formation of retrogenes. The two rounds of whole genome duplications in the vertebrate stem lineage gave rise to four arrestin paralogs. Surprisingly, visual arrestin ARR3 was lost in the mammalian clades Afrotheria and Xenarthra. Duplications in specific clades, on the other hand, must have given rise to new paralogs that show signatures of diversification in functional elements important for receptor binding and phosphate sensing. CONCLUSION: The current study traces the functional evolution of deuterostome arrestins in unprecedented detail. Based on a precise re-annotation of the exon-intron structure at nucleotide resolution, we infer the gain and loss of paralogs and patterns of conservation, co-variation and selection.
[Mh] Termos MeSH primário: Arrestinas/genética
Evolução Molecular
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Fosforilação
Ligação Proteica
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arrestins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1186/s12862-017-1001-4


  5 / 2063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28646018
[Au] Autor:Zhang F; Gannon M; Chen Y; Zhou L; Jiao K; Wang Q
[Ad] Endereço:Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
[Ti] Título:The amyloid precursor protein modulates α -adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment.
[So] Source:FASEB J;31(10):4434-4446, 2017 Oct.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The amyloid precursor protein (APP) has long been appreciated for its role in Alzheimer's disease (AD) pathology. However, less is known about the physiologic function of APP outside of AD. Particularly, whether and how APP may regulate functions of cell surface receptors, including GPCRs, remains largely unclear. In this study, we identified a novel direct interaction between APP and the α -adrenergic receptor (α AR) that occurs at the intracellular domains of both proteins. The APP interaction with α AR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor. Consequently, the presence of APP attenuates α AR internalization and desensitization, which are arrestin-dependent processes. Furthermore, in neuroblastoma neuro-2A cells and primary superior cervical ganglion neurons, where APP is highly expressed, the lack of APP leads to a dramatic increase in plasma membrane recruitment of endogenous arrestin 3 following α AR activation. Concomitantly, agonist-induced internalization of α AR is significantly enhanced in these neuronal cells. Our study provided the first evidence that APP fine tunes GPCR signaling and trafficking. Given the important role of α AR in controlling norepinephrine release and response, this novel regulation of α AR by APP may have an impact on modulation of noradrenergic activity and sympathetic tone.-Zhang, F., Gannon, M., Chen, Y., Zhou, L., Jiao, K., Wang, Q. The amyloid precursor protein modulates α -adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment.
[Mh] Termos MeSH primário: Arrestinas/metabolismo
Endocitose/efeitos dos fármacos
Neurônios/metabolismo
Receptores Adrenérgicos alfa 2/metabolismo
beta-Arrestina 2/metabolismo
[Mh] Termos MeSH secundário: Doença de Alzheimer/metabolismo
Precursor de Proteína beta-Amiloide/metabolismo
Precursor de Proteína beta-Amiloide/farmacologia
Animais
Endocitose/fisiologia
Camundongos
Transporte Proteico/fisiologia
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adra2a protein, mouse); 0 (Amyloid beta-Protein Precursor); 0 (Arrestins); 0 (Receptors, Adrenergic, alpha-2); 0 (arrestin3); 0 (beta-Arrestin 2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201700346R


  6 / 2063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28536260
[Au] Autor:Vishnivetskiy SA; Lee RJ; Zhou XE; Franz A; Xu Q; Xu HE; Gurevich VV
[Ad] Endereço:From Vanderbilt University, Nashville, Tennessee 37232.
[Ti] Título:Functional role of the three conserved cysteines in the N domain of visual arrestin-1.
[So] Source:J Biol Chem;292(30):12496-12502, 2017 Jul 28.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Arrestins specifically bind active and phosphorylated forms of their cognate G protein-coupled receptors, blocking G protein coupling and often redirecting the signaling to alternative pathways. High-affinity receptor binding is accompanied by two major structural changes in arrestin: release of the C-tail and rotation of the two domains relative to each other. The first requires detachment of the arrestin C-tail from the body of the molecule, whereas the second requires disruption of the network of charge-charge interactions at the interdomain interface, termed the polar core. These events can be facilitated by mutations destabilizing the polar core or the anchoring of the C-tail that yield "preactivated" arrestins that bind phosphorylated and unphosphorylated receptors with high affinity. Here we explored the functional role in arrestin activation of the three native cysteines in the N domain, which are conserved in all arrestin subtypes. Using visual arrestin-1 and rhodopsin as a model, we found that substitution of these cysteines with serine, alanine, or valine virtually eliminates the effects of the activating polar core mutations on the binding to unphosphorylated rhodopsin while only slightly reducing the effects of the C-tail mutations. Thus, these three conserved cysteines play a role in the domain rotation but not in the C-tail release.
[Mh] Termos MeSH primário: Arrestinas/química
Arrestinas/metabolismo
Cisteína/metabolismo
[Mh] Termos MeSH secundário: Animais
Arrestinas/genética
Cisteína/genética
Mutação
Fosforilação
Domínios Proteicos
Coelhos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arrestins); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.790386


  7 / 2063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28419873
[Au] Autor:Zurkovsky L; Sedaghat K; Ahmed MR; Gurevich VV; Gurevich EV
[Ad] Endereço:Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
[Ti] Título:Arrestin-2 and arrestin-3 differentially modulate locomotor responses and sensitization to amphetamine.
[So] Source:Neuropharmacology;121:20-29, 2017 Jul 15.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Arrestins play a prominent role in shutting down signaling via G protein-coupled receptors. In recent years, a signaling role for arrestins independent of their function in receptor desensitization has been discovered. Two ubiquitously expressed arrestin isoforms, arrestin-2 and arrestin-3, perform similarly in the desensitization process and share many signaling functions, enabling them to substitute for one another. However, signaling roles specific to each isoform have also been described. Mice lacking arrestin-3 (ARR3KO) were reported to show blunted acute responsiveness to the locomotor stimulatory effect of amphetamine (AMPH). It has been suggested that mice with deletion of arrestin-2 display a similar phenotype. Here we demonstrate that the AMPH-induced locomotion of male ARR3KO mice is reduced over the 7-day treatment period and during AMPH challenge after a 7-day withdrawal. The data are consistent with impaired locomotor sensitization to AMPH and suggest a role for arrestin-3-mediated signaling in the sensitization process. In contrast, male ARR2KO mice showed enhanced early responsiveness to AMPH and the lack of further sensitization, suggesting a role for impaired receptor desensitization. The comparison of mice possessing one allele of arrestin-3 and no arrestin-2 with ARR2KO littermates revealed reduced activity of the former line, consistent with a contribution of arrestin-3-mediated signaling to AMPH responses. Surprisingly, ARR3KO mice with one arrestin-2 allele showed significantly reduced locomotor responses to AMPH combined with lower novelty-induced locomotion, as compared to the ARR3KO line. These data suggest that one allele of arrestin-2 is unable to support normal locomotor behavior due to signaling and/or developmental defects.
[Mh] Termos MeSH primário: Anfetamina/farmacologia
Arrestinas/metabolismo
Estimulantes do Sistema Nervoso Central/farmacologia
Locomoção/efeitos dos fármacos
beta-Arrestina 1/metabolismo
[Mh] Termos MeSH secundário: Análise de Variância
Animais
Arrestinas/genética
Locomoção/genética
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fatores de Tempo
beta-Arrestina 1/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arrestins); 0 (Central Nervous System Stimulants); 0 (arrestin 4 protein, mouse); 0 (beta-Arrestin 1); CK833KGX7E (Amphetamine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE


  8 / 2063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28298493
[Au] Autor:Ho HC; MacGurn JA; Emr SD
[Ad] Endereço:Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853.
[Ti] Título:Deubiquitinating enzymes Ubp2 and Ubp15 regulate endocytosis by limiting ubiquitination and degradation of ARTs.
[So] Source:Mol Biol Cell;28(9):1271-1283, 2017 May 01.
[Is] ISSN:1939-4586
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Endocytic down-regulation of cell-surface proteins is a fundamental cellular process for cell survival and adaptation to environmental stimuli. Ubiquitination of cargo proteins serves as the sorting signal for downstream trafficking and relies on the arrestin-related trafficking adaptor (ART)-Rsp5 ubiquitin ligase adaptor network in yeast. Hence proper regulation of the abundance and activity of these ligase-adaptor complexes is critical for main-tenance of optimal plasma membrane protein composition. Here we report that the stability of ARTs is regulated by the deubiquitinating enzymes (DUBs) Ubp2 and Ubp15. By counteracting the E3 ubiquitin ligase Rsp5, Ubp2 and Ubp15 prevent hyperubiquitination and proteasomal degradation of ARTs. Specifically, we show that loss of both Ubp2 and Ubp15 results in a defect in Hxt6 endocytosis associated with Art4 instability. Our results uncover a novel function for DUBs in the endocytic pathway by which Ubp2 and Ubp15 positively regulate the ART-Rsp5 network.
[Mh] Termos MeSH primário: Enzimas Desubiquitinantes/metabolismo
Enzimas Desubiquitinantes/fisiologia
Endopeptidases/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Arrestinas/metabolismo
Membrana Celular/metabolismo
Endocitose/fisiologia
Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo
Ligação Proteica
Transporte Proteico
Saccharomyces cerevisiae/metabolismo
Ubiquitina/metabolismo
Complexos Ubiquitina-Proteína Ligase/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
Ubiquitinação/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arrestins); 0 (Endosomal Sorting Complexes Required for Transport); 0 (Saccharomyces cerevisiae Proteins); 0 (Ubiquitin); EC 2.3.2.23 (Ubiquitin-Protein Ligase Complexes); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 3.4.- (Endopeptidases); EC 3.4.19.12 (Deubiquitinating Enzymes); EC 3.4.99.- (Ubp15 protein, S cerevisiae); EC 3.4.99.- (ubiquitin-Nalpha-protein hydrolase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1091/mbc.E17-01-0008


  9 / 2063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28291835
[Au] Autor:Carroll SH; Zhang E; Wang BF; LeClair KB; Rahman A; Cohen DE; Plutzky J; Patwari P; Lee RT
[Ad] Endereço:Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, United States of America.
[Ti] Título:Adipocyte arrestin domain-containing 3 protein (Arrdc3) regulates uncoupling protein 1 (Ucp1) expression in white adipose independently of canonical changes in ß-adrenergic receptor signaling.
[So] Source:PLoS One;12(3):e0173823, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adaptive thermogenesis and cold-induced activation of uncoupling protein 1 (Ucp1) in brown adipose tissue in rodents is well-described and attributed to sympathetic activation of ß-adrenergic signaling. The arrestin domain containing protein Arrdc3 is a regulator of obesity in mice and also appears linked to obesity in humans. We generated a mouse with conditional deletion of Arrdc3, and here we present evidence that genetic ablation of Arrdc3 specifically in adipocytes results in increased Ucp1 expression in subcutaneous and parametrial adipose tissue. Although this increase in expression did not correspond with significant changes in body weight or energy expenditure, adipocyte-specific Arrdc3-null mice had improved glucose tolerance. It was previously hypothesized that Arrdc3 ablation leads to increased ß-adrenergic receptor sensitivity; however, in vitro experiments show that Arrdc3-null adipocytes responded to ß-adrenergic receptor agonist with decreased Ucp1 levels. Additionally, canonical ß-adrenergic receptor signaling was not different in Arrdc3-null adipocytes. These data reveal a role for Arrdc3 in the regulation of Ucp1 expression in adipocytes. However, this adipocyte effect is insufficient to generate the obesity-resistant phenotype of mice with ubiquitous deletion of Arrdc3, indicating a likely role for Arrdc3 in cells other than adipocytes.
[Mh] Termos MeSH primário: Tecido Adiposo Branco/metabolismo
Arrestinas/fisiologia
Receptores Adrenérgicos beta/metabolismo
Transdução de Sinais
Proteína Desacopladora 1/metabolismo
[Mh] Termos MeSH secundário: Animais
Arrestinas/genética
Composição Corporal
Camundongos
Camundongos Knockout
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ARRDC3 protein, mouse); 0 (Arrestins); 0 (Receptors, Adrenergic, beta); 0 (Ucp1 protein, mouse); 0 (Uncoupling Protein 1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173823


  10 / 2063 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28228552
[Au] Autor:Kumari P; Srivastava A; Ghosh E; Ranjan R; Dogra S; Yadav PN; Shukla AK
[Ad] Endereço:Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
[Ti] Título:Core engagement with ß-arrestin is dispensable for agonist-induced vasopressin receptor endocytosis and ERK activation.
[So] Source:Mol Biol Cell;28(8):1003-1010, 2017 Apr 15.
[Is] ISSN:1939-4586
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:G protein-coupled receptors (GPCRs) exhibit highly conserved activation and signaling mechanisms by which agonist stimulation leads to coupling of heterotrimeric G proteins and generation of second messenger response. This is followed by receptor phosphorylation, primarily in the carboxyl terminus but also in the cytoplasmic loops, and subsequent binding of arrestins. GPCRs typically recruit arrestins through two different sets of interactions, one involving phosphorylated receptor tail and the other mediated by the receptor core. The engagement of both set of interactions (tail and core) is generally believed to be necessary for arrestin-dependent functional outcomes such as receptor desensitization, endocytosis, and G protein-independent signaling. Here we demonstrate that a vasopressin receptor (V R) mutant with truncated third intracellular loop (V R ) can interact with ß-arrestin 1 (ßarr1) only through the phosphorylated tail without engaging the core interaction. Of interest, such a partially engaged V R -ßarr1 complex can efficiently interact with clathrin terminal domain and ERK2 MAPK in vitro. Furthermore, this core interaction-deficient V R mutant exhibits efficient endocytosis and ERK activation upon agonist stimulation. Our data suggest that core interaction with ßarr is dispensable for V R endocytosis and ERK activation and therefore provide novel insights into refining the current understanding of functional requirements in biphasic GPCR-ßarr interaction.
[Mh] Termos MeSH primário: Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Receptores de Vasopressinas/metabolismo
beta-Arrestina 1/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Arrestinas/metabolismo
Clatrina/metabolismo
Endocitose
Ativação Enzimática
Proteínas de Ligação ao GTP/metabolismo
Células HEK293
Seres Humanos
Sistema de Sinalização das MAP Quinases
Fosforilação
Ligação Proteica
Receptores Acoplados a Proteínas-G/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ARRB1 protein, human); 0 (Arrestins); 0 (Clathrin); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Vasopressin); 0 (beta-Arrestin 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 3.6.1.- (GTP-Binding Proteins)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170224
[St] Status:MEDLINE
[do] DOI:10.1091/mbc.E16-12-0818



página 1 de 207 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde