Journal of receptor and signal transduction research最新文献

{"title":"Cross-talk between protein kinase A and the MAPK-activated protein kinases RSK1 and MK5.","authors":"Sergiy Kostenko,&nbsp;Alexey Shiryaev,&nbsp;Gianina Dumitriu,&nbsp;Nancy Gerits,&nbsp;Ugo Moens","doi":"10.3109/10799893.2010.515593","DOIUrl":"https://doi.org/10.3109/10799893.2010.515593","url":null,"abstract":"<p><p>Typical mammalian mitogen-activated protein kinase (MAPK) pathways consist of a cascade of three consecutive phosphorylation events exerted by a MAPK kinase kinase (MAPKKK), a MAPK kinase (MAPKK), and finally a MAPK. MAPKs not only target non-protein kinase substrates, they can also phosphorylate other protein kinases designated as MAPK-activated protein kinases (MAPKAPK). The MAPKAPK family includes the ribosomal-S6-kinases (RSK1-4), the MAPK-interacting kinases (MNK1 and 2), the mitogen-and stress-activated kinases (MSK1 and 2), and the MAPKAPK (MK2, 3, and 5) subfamilies. Although several reports indicate extensive cross-talk between the MAPK and protein kinase A (PKA) pathways, evidence of a direct interaction at the level of the MAPKAPK only appeared recently. The MAPKAPKs RSK1 and MK5 can bind to PKA, but the features of these interactions are distinct. This review discusses the different characteristics of regulating the activity and subcellular localization of MK5 and RSK1 by PKA and the functional implications of these interactions.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2011-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2010.515593","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40076042","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":"Protein tyrosine nitration in cellular signal transduction pathways.","authors":"Vasily A Yakovlev,&nbsp;Ross B Mikkelsen","doi":"10.3109/10799893.2010.513991","DOIUrl":"https://doi.org/10.3109/10799893.2010.513991","url":null,"abstract":"<p><p>How specificity and reversibility in tyrosine nitration are defined biologically in cellular systems is poorly understood. As more investigations identify proteins involved in cell regulatory pathways in which only a small fraction of that protein pool is modified by nitration to affect cell function, the mechanisms of biological specificity and reversal should come into focus. In this review experimental evidence has been summarized to suggest that tyrosine nitration is a highly selective modification and under certain physiological conditions fulfills the criteria of a physiologically relevant signal. It can be specific, reversible, occurs on a physiological time scale, and, depending on a target, can result in either activation or inhibition.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"420-9"},"PeriodicalIF":2.8,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2010.513991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40069561","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":"Dimerization of G protein-coupled purinergic receptors: increasing the diversity of purinergic receptor signal responses and receptor functions.","authors":"Hiroyasu Nakata,&nbsp;Tokiko Suzuki,&nbsp;Kazunori Namba,&nbsp;Koshi Oyanagi","doi":"10.3109/10799893.2010.509729","DOIUrl":"https://doi.org/10.3109/10799893.2010.509729","url":null,"abstract":"<p><p>It is well accepted that G protein-coupled receptors (GPCRs) arrange into dimers or higher-order oligomers that may modify various functions of GPCRs. GPCR-type purinergic receptors (i.e. adenosine and P2Y receptors) tend to form heterodimers with GPCRs not only of the different families but also of the same purinergic receptor families, leading to alterations in functional properties. In the present review, we focus on current knowledge of the formation of heterodimers between metabotropic purinergic receptors that activate novel functions in response to extracellular nucleosides/nucleotides, revealing that the dimerization seems to be employed for 'fine-tuning' of purinergic signaling. Thus, the relationship between adenosine and adenosine triphosphate is likely to be more and more intimate than simply being a metabolite of the other.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"337-46"},"PeriodicalIF":2.8,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2010.509729","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40069560","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 dopamine D(4) receptor, the ultimate disordered protein.","authors":"Amina S Woods","doi":"10.3109/10799893.2010.513842","DOIUrl":"10.3109/10799893.2010.513842","url":null,"abstract":"<p><p>The human D4 dopamine receptor is a synaptic neurotransmitter receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its structure makes it a very unusual and interesting G protein-coupled receptor (GPCR) as it has several polymorphic variants of its gene in the region encoding the third intracellular loop (IL3). This region contains from two to seven or more similar 48 base pair repeats. These repeats cause this protein to have a very high disorder index and this, in turn, makes it very interactive with other proteins. Among GPCRs in general, the unusually proline-rich IL3 is unique to the D4 receptor (D4R). We believe that, as in the D2R, this region of the receptor plays a role in it's interaction with other receptors.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"331-6"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953771/pdf/nihms236756.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40065451","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":"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, Luigi F Agnati, Marc Caron, Bertil Fredholm, Diego Guidoli, Brian Kobilka, Robert W Lefkowitz, Martin Lohse, Amina Woods, Kjell Fuxe","doi":"10.3109/10799893.2010.512438","DOIUrl":"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":2.3,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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}