Sarah Cardoso, Stephen P Robertson, Philip B Daniel
{"title":"TGFBR1 mutations associated with Loeys-Dietz syndrome are inactivating.","authors":"Sarah Cardoso, Stephen P Robertson, Philip B Daniel","doi":"10.3109/10799893.2012.664553","DOIUrl":"https://doi.org/10.3109/10799893.2012.664553","url":null,"abstract":"<p><p>To assess the effect of Loeys-Dietz syndrome (LDS) mutations affecting TGFΒR1 a selection of seven disease-associated amino acid substitutions were introduced into wild type TGFβR1 and constitutively active TGFβR1(T204D). Receptor function was tested by co-transfection with a luciferase reporter or EGFP-tagged SMAD2 in HEK293 cells. All of the mutations were found to be inactivating for canonical TGF-β signaling. Differences in residual activity were not found to correlate with disease subtype. In co-transfection experiments with equal amounts wild-type receptor, the LDS mutations were found to confer a modest dominant negative effect. These results are discussed in relation to LDS and the related Marfan syndrome.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"150-5"},"PeriodicalIF":2.8,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2012.664553","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40161810","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}
M D Mubashshir, Fraz Ahmed, Safia Sumoona, Mohd Ovais
{"title":"Analyzing the responses of saccharin in context with melatonin receptors on the melanophores of the fish Labeo rohita (Ham.).","authors":"M D Mubashshir, Fraz Ahmed, Safia Sumoona, Mohd Ovais","doi":"10.3109/10799893.2012.660533","DOIUrl":"https://doi.org/10.3109/10799893.2012.660533","url":null,"abstract":"<p><p>The hormone melatonin regulates the biological clock and assist in various other physiologies of vertebrates. Present work is intended to check the affinity of saccharin towards the melatonin receptors and the possible role of saccharin interference in the melatonin physiology. The present in vitro study is based on the working model of isolated scale melanophores in the dorso-lateral region of Labeo rohita. The pigment cells were incubated in the agonist and the antagonists within a limited time frame and subsequently their Melanophore Size Index (MSI) were calculated. The inferences were drafted through the observed signal transduction upshots in pigment translocations within the melanophores. Saccharin, in a wide dose range, has consistently induced a concentration-related aggregation similar to the aggregatory effect as shown by melatonin on the melanophores. Binding of saccharin with the receptors and eliciting its aggregatory effect is partially dependent on the release of neurotransmitters. The aggregatory effects were found to be significantly blocked by luzindole, K185, and prazosin, which are the potent melatonin receptor blockers, at the higher concentrations of saccharin. Hence, all the three subtypes of melatonin receptors viz. MT₁, MT₂, and MT₃ are participating in saccharin-mediated aggregations. Blocking by neomycin shows that Ca²⁺ ions are very crucial in dispensing the aggregatory effect of the sweetener. This research demands that an intensive and careful thorough study should be made about saccharin, specifically its effects upon melatonin physiology, before its unwarranted use as the food ingredients for human use.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"114-9"},"PeriodicalIF":2.8,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2012.660533","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40152982","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}
Hidetoshi Asai, Yumi Watanabe, Rikako Yamauchi-Kohno, Osamu Doi
{"title":"Reversal of hemorrhagic shock in rats using the metabolically stable thyrotropin-releasing hormone analog taltirelin hydrate.","authors":"Hidetoshi Asai, Yumi Watanabe, Rikako Yamauchi-Kohno, Osamu Doi","doi":"10.3109/10799893.2011.625427","DOIUrl":"https://doi.org/10.3109/10799893.2011.625427","url":null,"abstract":"<p><p>We investigated the effect of taltirelin hydrate ((−)-N-[(S)-hexahydro-1-methyl- 2,6-dioxo-4-pyrimidinyl-carbonyl]-L-histidyl-L-prolinamide tetrahydrate; taltirelin), a metabolically stable thyrotropin-releasing hormone (TRH) analog, on circulatory function, respiratory function, and viable time after bleeding in urethane-anesthetized rats. Massive volume-controlled bleeding caused marked reductions in mean arterial pressure (MAP) and respiratory rate (RR). The vital signs of control rats were lost within an average of 23 min after bleeding. Intravenous administration of taltirelin (0.03−0.3 mg/kg) and TRH (1 and 3 mg/kg) immediately after bleeding accelerated recovery of MAP and RR, and prolonged viable time in a dose-dependent manner. The potency of taltirelin in accelerating MAP and RR recovery and prolonging viable time was higher when compared with that of TRH. In addition, recovery of MAP and RR and the extension of viable time by taltirelin were inhibited by preintraperitoneal administration of atropine sulfate, which is a centrally acting muscarinic antagonist, but not by that of atropine methylbromide, which is a peripherally acting muscarinic antagonist. Taltirelin also recovered decreased arterial pH, bicarbonate ions, and base excess, and prevented a decrease in arterial oxygen saturation. In conclusion, the anti-shock effect of taltirelin was more potent than that of TRH. Taltirelin activity was mediated by the central muscarinic cholinergic system. In addition, taltirelin also corrected metabolic acidosis. These results suggest that taltirelin could be useful in the treatment of hypovolemic shock.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"416-22"},"PeriodicalIF":2.8,"publicationDate":"2011-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2011.625427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40121448","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":"Receptor tyrosine kinases: from biology to pathology.","authors":"Mouna Choura, Ahmed Rebaï","doi":"10.3109/10799893.2011.625425","DOIUrl":"https://doi.org/10.3109/10799893.2011.625425","url":null,"abstract":"<p><p>Receptor tyrosine kinases (RTKs) are transmembrane proteins involved in the control of fundamental cellular processes in metazoans. RTKs possess a general structure that includes an extracellular domain, a transmembrane domain and a highly conserved tyrosine kinase domain. RTKs are classified according to their variable extracellular ligand-binding domain. Studies of human RTK members have yielded a wealth of information elucidating their importance. Improper functioning of these enzymes due to mutations, mainly in the kinase domain, is often manifested in various human diseases and is known to be involved in several types of cancer. Here we summarize most of human RTKs, their cognate ligands, as well as related diseases and discuss the eventual use of certain RTKs as new therapeutic targets.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"387-94"},"PeriodicalIF":2.8,"publicationDate":"2011-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2011.625425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40116305","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":"Cross-talk between protein kinase A and the MAPK-activated protein kinases RSK1 and MK5.","authors":"Sergiy Kostenko, Alexey Shiryaev, Gianina Dumitriu, Nancy Gerits, 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, 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}
Hiroyasu Nakata, Tokiko Suzuki, Kazunori Namba, Koshi Oyanagi
{"title":"Dimerization of G protein-coupled purinergic receptors: increasing the diversity of purinergic receptor signal responses and receptor functions.","authors":"Hiroyasu Nakata, Tokiko Suzuki, Kazunori Namba, 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}
Terry Kenakin, Luigi F Agnati, Marc Caron, Bertil Fredholm, Diego Guidoli, Brian Kobilka, Robert W Lefkowitz, Martin Lohse, Amina Woods, Kjell Fuxe
{"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":"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}