Journal of receptor and signal transduction research最新文献

{"title":"Theme and variations on kinetics of GPCR activation/deactivation.","authors":"Jean-Pierre Vilardaga","doi":"10.3109/10799893.2010.509728","DOIUrl":"10.3109/10799893.2010.509728","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) initiate intracellular signaling pathways in response to physiologically and medically important extracellular ligands such as peptide and large glycoprotein hormones, neurotransmitters, sensory stimuli (odorant and taste molecules, light), calcium, l-amino acids, and are the target of many clinical drugs. The conversion of these extracellular stimuli into intracellular signals involves sequential and reversible reactions that initially take place at the plasma membrane. These reactions are mediated not only by dynamic interactions between ligands, receptors and heterotrimeric G proteins, but also by conformational changes associated with the activation/deactivation process of each protein. This review discusses the kinetic characteristics and rate-limiting reactions engaged in signal propagation that are involved in systems as diverse as neurotransmitter and hormonal signaling, and that have been recorded in live cells by Förster resonance energy transfer (FRET) approaches.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"304-12"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380358/pdf/nihms267600.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40065446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International Workshop at the Nobel Forum, Karolinska Institutet on G protein-coupled receptors: finding the words to describe monomers, oligomers, and their molecular mechanisms and defining their meaning. Can a consensus be reached?","authors":"Terry Kenakin,&nbsp;Luigi F Agnati,&nbsp;Marc Caron,&nbsp;Bertil Fredholm,&nbsp;Diego Guidoli,&nbsp;Brian Kobilka,&nbsp;Robert W Lefkowitz,&nbsp;Martin Lohse,&nbsp;Amina Woods,&nbsp;Kjell Fuxe","doi":"10.3109/10799893.2010.512438","DOIUrl":"https://doi.org/10.3109/10799893.2010.512438","url":null,"abstract":"<p><p>A meeting was held May 19, 2010 at the Karolinski Institute on Nomenclature in Pharmacology. This meeting occurred in conjunction with the Symposium The Changing World of G Protein Coupled Receptors: From Monomers to Dimers and Receptor Mosaics (Higher-order Oligomers) held the previous day at the Royal Swedish Academy of Science. Two broad topics of nomenclature were discussed; ligand nomenclature and the definition of 'receptor-receptor' interactions. This paper summarizes discussions on these topics along with a consensus definition of the term 'receptor-receptor' interaction.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"284-6"},"PeriodicalIF":2.8,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2010.512438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40083622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G protein coupled receptors as allosteric proteins and the role of allosteric modulators.","authors":"Terry Kenakin","doi":"10.3109/10799893.2010.503964","DOIUrl":"https://doi.org/10.3109/10799893.2010.503964","url":null,"abstract":"<p><p>Seven transmembrane receptors (7TMRs) are proteins that convey signals through changes in conformation. These conformations are stabilized by external molecules (i.e. agonists, antagonists, modulators) and act upon other bodies (termed 'guests') which can be other molecules in the extracellular space, or proteins along the plane of the membrane (receptor oligomerization) or signaling proteins in the cytosol (i.e. G protein, β-arrestin). These elements comprise allosteric systems and a great deal of 7TMR pharmacology can be considered in terms of allosteric behavior. Allosteric ligands acting on 7TMRs possess four unique behaviors that can be valuable therapeutically; (1) the ability to alter the interaction of very large proteins, (2) probe dependence, (3) saturable effect, and (4) induction of separate changes in affinity and efficacy of other ligands. Two of these behaviors (namely probe dependence for CCR5-based HIV-1 entry inhibitors and functional selectivity for biased agonism) will be highlighted with examples.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"313-21"},"PeriodicalIF":2.8,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2010.503964","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40084633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The changing world of G protein-coupled receptors.","authors":"Kjell Fuxe,&nbsp;Terrence Kenakin","doi":"10.3109/10799893.2010.507367","DOIUrl":"https://doi.org/10.3109/10799893.2010.507367","url":null,"abstract":"G protein-coupled receptors, is based on a Royal Swedish Academy of Sciences symposium held in Stockholm, Sweden on May 18 2010 organized by Dr K Fuxe under the theme “The changing world of G protein-coupled receptors: From monomers to dimers and receptor mosaics (higher order oligomers)”. The first section of the issue introduces the GPCR field and its novel terminology. The Kenakin et al. paper summarizes a workshop held on GPCRs, and receptor–receptor interactions and their terminology, held at Nobel Forum, Karolinska Institutet on May 19 2010, during which the definition of the “receptor–receptor interactions” was agreed upon. The early work on negative cooperativity and neuropeptide-monoamine receptor–receptor interactions in the CNS is reported to give some of the first indications of the existence of homodimers and heterodimers of GPCRs, respectively, and the field began to expand from monomers into dimers and receptor mosaics. It is also emphasized that the existence of receptor heteromers with allosteric receptor–receptor interactions increases the diversity of GPCR recognition and signaling. The molecular phenomenon of receptor–receptor interactions is proposed to give a better understanding of brain function through molecular integration of signals. An alteration in specific receptor– receptor interactions is in fact considered to play a role in pathogenic mechanisms leading to several diseases, inter alia Parkinson’s disease, hypertension, schizophrenia, addiction and depression. Therefore, pharmacological targeting of receptor–receptor interactions in heteromers is described as an important area for developing more selective drugs including bivalent compounds and optimal types of combined treatments. The second section covers the dynamics of GPCRs. Vilardaga reviews the kinetics of GPCR activation/ deactivation including the importance of the associated conformational changes in these processes, and Kenakin reviews the GPCR and their assemblies as representing allosteric systems where the allosteric mechanisms have a major role in determining their pharmacology. He clearly outlines the allosteric modulators of GPCRs as highly valuable therapeutics. The third section gives the state of the art on GPCR heterodimers and receptor mosaics of different types of GPCRs, and their receptor–receptor interactions. Ciruela et al. report inter alia, the impact of heteromerization on receptor biosynthesis, plasma membrane diffusion or velocity, and pharmacology, and discuss the molecular basis of the receptor interface in the GPCR oligomers. It is underlined that the challenge still remains to give direct evidence for receptor–receptor interactions in heteromers in native tissue. Woods et al. summarize the overall evidence for the importance of electrostatic receptor–receptor interactions in the formation of the receptor interface in GPCR heteromers. Nakata et al. review their evidence for the ability of GPCR heterodimerization to increase the div","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"271"},"PeriodicalIF":2.8,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2010.507367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40083621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}