Receptors & clinical investigation最新文献

CD28 family of receptors inter-connect in the regulation of T-cells CD28受体家族在t细胞调控中相互连接

Receptors & clinical investigation Pub Date : 2017-09-25 DOI: 10.14800/rci.1581

Janna Krueger, Felix Jules, S. Rieder, C. Rudd

引用次数: 4

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) promote neurorepair in the ischemic brain 尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)促进缺血性脑的神经修复

Receptors & clinical investigation Pub Date : 2017-06-06 DOI: 10.14800/RCI.1552

Paola Merino, Ariel Diaz, M. Yepes

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引用次数: 20

Bacterial superantigen toxins induce a lethal cytokine storm by enhancing B7-2/CD28 costimulatory receptor engagement, a critical immune checkpoint. 细菌超抗原毒素通过增强B7-2/CD28共刺激受体结合(一个关键的免疫检查点)诱导致命的细胞因子风暴。

Receptors & clinical investigation Pub Date : 2017-01-30 DOI: 10.14800/rci.1500

R. Kaempfer, Andrey Popugailo, R. Levy, G. Arad, D. Hillman, Ziv Rotfogel

{"title":"Bacterial superantigen toxins induce a lethal cytokine storm by enhancing B7-2/CD28 costimulatory receptor engagement, a critical immune checkpoint.","authors":"R. Kaempfer, Andrey Popugailo, R. Levy, G. Arad, D. Hillman, Ziv Rotfogel","doi":"10.14800/rci.1500","DOIUrl":"https://doi.org/10.14800/rci.1500","url":null,"abstract":"Formation of the costimulatory axis between the B7-2 and CD28 coreceptors is critical for T-cell activation. Superantigens, Gram-positive bacterial virulence factors, cause toxic shock and sepsis by hyperinducing inflammatory cytokines. We report a novel role for costimulatory receptors CD28 and B7-2 as obligatory receptors for superantigens, rendering them therapeutic targets. We show that by engaging not only CD28 but also its coligand B7-2 directly, superantigens potently enhance the interaction between B7-2 and CD28, inducing thereby T-cell hyperactivation. Using a conserved twelve amino-acid domain, superantigens engage both B7-2 and CD28 at their homodimer interfaces, sites far removed from where these receptors interact, implying that inflammatory signaling can be controlled through the receptor homodimer interfaces. Short B7-2 and CD28 dimer interface mimetic peptides bind diverse superantigens, prevent superantigen binding to cell-surface B7-2 or CD28, attenuate inflammatory cytokine overexpression, and protect mice from lethal superantigen challenge. Thus, superantigens induce a cytokine storm by mediating not only the interaction between MHC-II molecule and T-cell receptor but critically, by promoting B7-2/CD28 coreceptor engagement, forcing the principal costimulatory axis to signal excessively. Our findings highlight the B7/CD28 interaction as a bottleneck in signaling for expression of inflammatory cytokines. B7-2 and CD28 homodimer interface mimetic peptides prevent superantigen lethality by blocking the superantigen-host costimulatory receptor interaction.","PeriodicalId":74650,"journal":{"name":"Receptors & clinical investigation","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81483710","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}

引用次数: 10

G protein-coupled receptors mediate neural regulation of innate immune responses in caenorhabditis elegans. G蛋白偶联受体介导神经调节草履虫的先天性免疫反应。

Receptors & clinical investigation Pub Date : 2017-01-01 Epub Date: 2017-05-24 DOI: 10.14800/rci.1543

Yiyong Liu, Jingru Sun

引用次数: 0

An entry-competent intermediate state of the HIV-1 envelope glycoproteins. HIV-1包膜糖蛋白的进入性中间状态。

Receptors & clinical investigation Pub Date : 2017-01-01 Epub Date: 2017-05-24 DOI: 10.14800/rci.1544

Alon Herschhorn, Joseph Sodroski

{"title":"An entry-competent intermediate state of the HIV-1 envelope glycoproteins.","authors":"Alon Herschhorn, Joseph Sodroski","doi":"10.14800/rci.1544","DOIUrl":"https://doi.org/10.14800/rci.1544","url":null,"abstract":"The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) mediate viral entry and are the sole target of neutralizing antibodies. Recent studies show that the metastable HIV-1 Env trimer can transit among three conformational states: State 1, State 3, and State 2, corresponding to the \"closed\", \"open\" and intermediate conformations, respectively. During virus entry, binding to the CD4 receptor drives Env from state 1 to state 3. In the unliganded Env, transitions from the closed (State 1) conformation are restrained by intramolecular interactions among different Env residues, which regulate HIV-1 Env conformation. Releasing the specific restraints on State 1 Env leads to increased occupancy of State 2, which is a functional conformation on the entry pathway and an obligate intermediate between State 1 and State 3. Frequent sampling of intermediate State 2 allows HIV-1 to infect cells expressing low levels of CD4, and leads to resistance to several broadly neutralizing antibodies as well as small-molecule inhibitors. Recent findings provide new mechanistic insights into the function and inhibition of HIV-1 Env and will contribute to the development of new therapeutic and prophylactic interventions to combat HIV-1.","PeriodicalId":74650,"journal":{"name":"Receptors & clinical investigation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35206147","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}

引用次数: 9

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) promote neurorepair in the ischemic brain. 尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)促进缺血性脑的神经修复。

Receptors & clinical investigation Pub Date : 2017-01-01 Epub Date: 2017-06-06

Paola Merino, Ariel Diaz, Manuel Yepes

{"title":"Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) promote neurorepair in the ischemic brain.","authors":"Paola Merino, Ariel Diaz, Manuel Yepes","doi":"","DOIUrl":"","url":null,"abstract":"Despite the fact that ischemic stroke has been considered a leading cause of mortality in the world, recent advances in our understanding of the pathophysiological mechanisms underlying the ischemic injury and the treatment of acute ischemic stroke patients have led to a sharp decrease in the number of stroke deaths. However, this decrease in stroke mortality has also led to an increase in the number of patients that survive the acute ischemic injury with different degrees of disability. Unfortunately, to this date we do not have an effective therapeutic strategy to promote neurological recovery in these growing population of stroke survivors. Cerebral ischemia not only causes the destruction of a large number of axons and synapses but also activates endogenous mechanisms that promote the recovery of those neurons that survive its harmful effects. Here we review experimental evidence indicating that one of these mechanisms of repair is the binding of the serine proteinase urokinase-type plasminogen activator (uPA) to its receptor (uPAR) in the growth cones of injured axons. Indeed, the binding of uPA to uPAR in the periphery of growth cones of injured axons induces the recruitment of β1-integrin to the plasma membrane, β1-integrin-mediated activation of the small Rho GTPase Rac1, and Rac1-induced axonal regeneration. Furthermore, we found that this process is modulated by the low density lipoprotein receptor-related protein (LRP1). The data reviewed here indicate that the uPA-uPAR-LRP1 system is a potential target for the development of therapeutic strategies to promote neurological recovery in acute ischemic stroke patients.","PeriodicalId":74650,"journal":{"name":"Receptors & clinical investigation","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35410631","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}

引用次数: 0

Bacterial superantigen toxins induce a lethal cytokine storm by enhancing B7-2/CD28 costimulatory receptor engagement, a critical immune checkpoint. 细菌超抗原毒素通过增强B7-2/CD28共刺激受体结合(一个关键的免疫检查点)诱导致命的细胞因子风暴。

Receptors & clinical investigation Pub Date : 2017-01-01 Epub Date: 2017-01-30

Raymond Kaempfer, Andrey Popugailo, Revital Levy, Gila Arad, Dalia Hillman, Ziv Rotfogel

{"title":"Bacterial superantigen toxins induce a lethal cytokine storm by enhancing B7-2/CD28 costimulatory receptor engagement, a critical immune checkpoint.","authors":"Raymond Kaempfer, Andrey Popugailo, Revital Levy, Gila Arad, Dalia Hillman, Ziv Rotfogel","doi":"","DOIUrl":"","url":null,"abstract":"Formation of the costimulatory axis between the B7-2 and CD28 coreceptors is critical for T-cell activation. Superantigens, Gram-positive bacterial virulence factors, cause toxic shock and sepsis by hyperinducing inflammatory cytokines. We report a novel role for costimulatory receptors CD28 and B7-2 as obligatory receptors for superantigens, rendering them therapeutic targets. We show that by engaging not only CD28 but also its coligand B7-2 directly, superantigens potently enhance the interaction between B7-2 and CD28, inducing thereby T-cell hyperactivation. Using a conserved twelve amino-acid domain, superantigens engage both B7-2 and CD28 at their homodimer interfaces, sites far removed from where these receptors interact, implying that inflammatory signaling can be controlled through the receptor homodimer interfaces. Short B7-2 and CD28 dimer interface mimetic peptides bind diverse superantigens, prevent superantigen binding to cell-surface B7-2 or CD28, attenuate inflammatory cytokine overexpression, and protect mice from lethal superantigen challenge. Thus, superantigens induce a cytokine storm by mediating not only the interaction between MHC-II molecule and T-cell receptor but critically, by promoting B7-2/CD28 coreceptor engagement, forcing the principal costimulatory axis to signal excessively. Our findings highlight the B7/CD28 interaction as a bottleneck in signaling for expression of inflammatory cytokines. B7-2 and CD28 homodimer interface mimetic peptides prevent superantigen lethality by blocking the superantigen-host costimulatory receptor interaction.","PeriodicalId":74650,"journal":{"name":"Receptors & clinical investigation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341606/pdf/nihms-848301.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34806099","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}

引用次数: 0

Physiological role of receptor activator nuclear factor-kB (RANK) in denervation-induced muscle atrophy and dysfunction. 受体激活因子核因子kb (RANK)在去神经支配诱导的肌肉萎缩和功能障碍中的生理作用。

Receptors & clinical investigation Pub Date : 2016-05-30 DOI: 10.14800/rci.1323

Sébastien S Dufresne, Antoine Boulanger-Piette, Sabrina Bossé, Jérôme Frenette

{"title":"Physiological role of receptor activator nuclear factor-kB (RANK) in denervation-induced muscle atrophy and dysfunction.","authors":"Sébastien S Dufresne, Antoine Boulanger-Piette, Sabrina Bossé, Jérôme Frenette","doi":"10.14800/rci.1323","DOIUrl":"https://doi.org/10.14800/rci.1323","url":null,"abstract":"The bone remodeling and homeostasis are mainly controlled by the receptor-activator of nuclear factor kB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin (OPG) pathway. While there is a strong association between osteoporosis and skeletal muscle dysfunction, the functional relevance of a particular biological pathway that synchronously regulates bone and skeletal muscle physiopathology remains elusive. Our recent article published in the American Journal of Physiology (Cell Physiology) showed that RANK is also expressed in fully differentiated C2C12 myotubes and skeletal muscles. We used the Cre-Lox approach to inactivate muscle RANK (RANKmko) and showed that RANK deletion preserves the force of denervated fast-twitch EDL muscles. However, RANK deletion had no positive impact on slow-twitch Sol muscles. In addition, denervating RANKmko EDL muscles induced an increase in the total calcium concentration ([CaT]), which was associated with a surprising decrease in SERCA activity. Interestingly, the levels of STIM-1, which mediates Ca2+ influx following the depletion of SR Ca2+ stores, were markedly higher in denervated RANKmko EDL muscles. We speculated that extracellular Ca2+ influx mediated by STIM-1 may be important for the increase in [CaT] and the gain of force in denervated RANKmko EDL muscles. Overall, these findings showed for the first time that the RANKL/RANK interaction plays a role in denervation-induced muscle atrophy and dysfunction.","PeriodicalId":74650,"journal":{"name":"Receptors & clinical investigation","volume":"3 2","pages":"e13231-e13236"},"PeriodicalIF":0.0,"publicationDate":"2016-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34325503","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}

引用次数: 13

Major vault protein in cardiac and smooth muscle 心脏和平滑肌中的主要拱顶蛋白

Receptors & clinical investigation Pub Date : 2016-05-23 DOI: 10.14800/RCI.1310

N. Shults, Dividutta Das, Yuichiro J. Suzuki

引用次数: 4

GRK2: putting the brakes on the circadian clock. GRK2:给生物钟踩刹车。

Receptors & clinical investigation Pub Date : 2016-02-01 DOI: 10.14800/rci.1175

Lucia Mendoza-Viveros, Arthur H Cheng, Hai-Ying M Cheng

{"title":"GRK2: putting the brakes on the circadian clock.","authors":"Lucia Mendoza-Viveros, Arthur H Cheng, Hai-Ying M Cheng","doi":"10.14800/rci.1175","DOIUrl":"https://doi.org/10.14800/rci.1175","url":null,"abstract":"G protein-coupled receptor kinases (GRKs) are a family of serine/threonine protein kinases that terminate G protein-coupled receptor (GPCR) signaling by phosphorylating the receptor and inducing its internalization. In addition to their canonical function, some GRKs can phosphorylate non-GPCR substrates and regulate GPCR signaling in a kinase-independent manner. GPCRs are abundantly expressed in the suprachiasmatic nucleus (SCN), a structure in the mammalian brain that serves as the central circadian pacemaker. Various facets of circadian timekeeping are under the influence of GPCR signaling, and thus are potential targets for GRK regulation. Despite this, little attention has been given to the role of GRKs in circadian rhythms. In this research highlight, we discuss our latest findings on the functional involvement of GRK2 in mammalian circadian timekeeping in the SCN. Using grk2 knockout mice, we demonstrate that GRK2 is critical for maintaining proper clock speed and ensuring that the clock is appropriately synchronized to environmental light cycles. Although grk2 deficiency expectedly alters the expression of a key GPCR in the SCN, our study also reveals that GRK2 has a more direct function that touches the heart of the circadian clock.","PeriodicalId":74650,"journal":{"name":"Receptors & clinical investigation","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830691/pdf/nihms5446.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34409856","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}

引用次数: 3