Objective To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-κB (NF-κB) signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell li...Objective To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-κB (NF-κB) signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell lines were transfected with plasmids expressing wild type TRAF2 or dominant negative TRAF2,TRAF2-shRNA,or TRAF6-shRNA. The activation of NF-κB was detected by Western blot,kinase assay,transfactor enzyme-linked immunosorbent assay (ELISA),and fluorescence resonance energy transfer (FRET). Analysis of the role of TRAF-2 and TRAF-6 in CD40-mediated NF-κB activity was examined following stimulation with recombinant CD154. Results TRAF2 induced activity of IκB-kinases (IKKα,IKKi/ε),phosphorylation of IκBα,as well as nuclear translocation and phosphorylation of p65/RelA. In contrast,TRAF6 strongly induced NF-κB activation and nuclear translocation of p65 as well as p50 and c-Rel. Engagement of CD154-induced nuclear translocation of p65 was inhibited by a TRAF6-shRNA,but conversely was enhanced by a TRAF2-shRNA. Examination of direct interactions between CD40 and TRAFs by FRET documented that both TRAF2 and TRAF6 directly interacted with CD40. However,the two TRAFs competed for CD40 binding. Conclusions These results indicate that TRAF2 can signal in human B cells,but it is not essential for CD40-mediated NF-κB activation. Moreover,TRAF2 can compete with TRAF6 for CD40 binding,and thereby limit the capacity of CD40 engagement to induce NF-κB activation.展开更多
G-protein coupled receptors(GPCRs)compromise the largest membrane protein superfamily which play vital roles in physiological and pathophysiological processes including energy homeostasis.Moreover,they also represent ...G-protein coupled receptors(GPCRs)compromise the largest membrane protein superfamily which play vital roles in physiological and pathophysiological processes including energy homeostasis.Moreover,they also represent the up-to-date most successful drug target.The gut hormone GPCRs,such as glucagon receptor and GLP-1 receptor,have been intensively studied for their roles in metabolism and respective drugs have developed for the treatment of metabolic diseases such as type 2 diabetes(T2D).Along with the advances of biomedical research,more GPCRs have been found to play important roles in the regulation of energy homeostasis from nutrient sensing,appetite control to glucose and fatty acid metabolism with various mechanisms.The investigation of their biological functions will not only improve our understanding of how our body keeps the balance of energy intake and expenditure,but also highlight the possible drug targets for the treatment of metabolic diseases.The present review summarizes GPCRs involved in the energy control with special emphasis on their pathophysiological roles in metabolic diseases and hopefully triggers more intensive and systematic investigations in the field so that a comprehensive network control of energy homeostasis will be revealed,and better drugs will be developed in the foreseeable future.展开更多
Organic electron acceptor materials play an important role in organic electronics.Recently,many organic electron acceptors have been developed,in which aromatic fused-imides have proved to be a promising family of exc...Organic electron acceptor materials play an important role in organic electronics.Recently,many organic electron acceptors have been developed,in which aromatic fused-imides have proved to be a promising family of excellent electron acceptors.We report the first synthesis of a novel aromatic fused-imide,acenaphtho[1,2-k]fluoranthene diimide derivative(AFI),using lithium-halogen exchange and Diels-Alder reactions.The construction of a large conjugated plane and the introduction of electron-withdrawing imide groups endow AFI with a low lowest unoccupied molecular orbital(LUMO)level of 3.80 e V.AFI exhibits a regular molecular arrangement and strong - interactions in the single-crystal structure,which indicates its potential application in organic electronic devices.Solar cell devices that were fabricated using AFI as the electron acceptor and P3HT as the electron donor achieved an energy conversion efficiency of 0.33%.展开更多
Stimulation of G protein-coupled receptors(GPCRs) can lead to the transactivation of the epidermal growth factor receptors(EGFR). The cross-communication between the two signaling pathways regulates several important ...Stimulation of G protein-coupled receptors(GPCRs) can lead to the transactivation of the epidermal growth factor receptors(EGFR). The cross-communication between the two signaling pathways regulates several important physiological or pathological processes. However, the molecule mechanism underlying EGFR transactivation remains poorly understood. Here, we aim to study the GPCR-mediated EGFR transactivation process using the single-molecule fluorescence imaging and tracking approach.We found that although EGFR existed as monomers at the plasma membrane of resting cells, they became dimers and thus diffused slower following the activation of β2-adrenergic receptor(β2-AR) by isoproterenol(ISO). We further proved thatβ2-AR-mediated changes of EGFR in stoichiometry and dynamics were mediated by Src kinase. Thus, the observations obtained via the single-molecule imaging and tracking methods shed new insights into the molecular mechanism of EGFR transactivation at single molecule level.展开更多
基金Supported by Key Projects of the National Science & Technology Pillar Program in the Eleventh Five-year Plan Period (2008-BAI59B02)
文摘Objective To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-κB (NF-κB) signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell lines were transfected with plasmids expressing wild type TRAF2 or dominant negative TRAF2,TRAF2-shRNA,or TRAF6-shRNA. The activation of NF-κB was detected by Western blot,kinase assay,transfactor enzyme-linked immunosorbent assay (ELISA),and fluorescence resonance energy transfer (FRET). Analysis of the role of TRAF-2 and TRAF-6 in CD40-mediated NF-κB activity was examined following stimulation with recombinant CD154. Results TRAF2 induced activity of IκB-kinases (IKKα,IKKi/ε),phosphorylation of IκBα,as well as nuclear translocation and phosphorylation of p65/RelA. In contrast,TRAF6 strongly induced NF-κB activation and nuclear translocation of p65 as well as p50 and c-Rel. Engagement of CD154-induced nuclear translocation of p65 was inhibited by a TRAF6-shRNA,but conversely was enhanced by a TRAF2-shRNA. Examination of direct interactions between CD40 and TRAFs by FRET documented that both TRAF2 and TRAF6 directly interacted with CD40. However,the two TRAFs competed for CD40 binding. Conclusions These results indicate that TRAF2 can signal in human B cells,but it is not essential for CD40-mediated NF-κB activation. Moreover,TRAF2 can compete with TRAF6 for CD40 binding,and thereby limit the capacity of CD40 engagement to induce NF-κB activation.
文摘G-protein coupled receptors(GPCRs)compromise the largest membrane protein superfamily which play vital roles in physiological and pathophysiological processes including energy homeostasis.Moreover,they also represent the up-to-date most successful drug target.The gut hormone GPCRs,such as glucagon receptor and GLP-1 receptor,have been intensively studied for their roles in metabolism and respective drugs have developed for the treatment of metabolic diseases such as type 2 diabetes(T2D).Along with the advances of biomedical research,more GPCRs have been found to play important roles in the regulation of energy homeostasis from nutrient sensing,appetite control to glucose and fatty acid metabolism with various mechanisms.The investigation of their biological functions will not only improve our understanding of how our body keeps the balance of energy intake and expenditure,but also highlight the possible drug targets for the treatment of metabolic diseases.The present review summarizes GPCRs involved in the energy control with special emphasis on their pathophysiological roles in metabolic diseases and hopefully triggers more intensive and systematic investigations in the field so that a comprehensive network control of energy homeostasis will be revealed,and better drugs will be developed in the foreseeable future.
基金financially supported by the National Basic Research Program of China(2013CB933501)the National Natural Science Foundation of Chinasupported by a General Financial Grant(2013M530135)from the China Postdoctoral Science Foundation
文摘Organic electron acceptor materials play an important role in organic electronics.Recently,many organic electron acceptors have been developed,in which aromatic fused-imides have proved to be a promising family of excellent electron acceptors.We report the first synthesis of a novel aromatic fused-imide,acenaphtho[1,2-k]fluoranthene diimide derivative(AFI),using lithium-halogen exchange and Diels-Alder reactions.The construction of a large conjugated plane and the introduction of electron-withdrawing imide groups endow AFI with a low lowest unoccupied molecular orbital(LUMO)level of 3.80 e V.AFI exhibits a regular molecular arrangement and strong - interactions in the single-crystal structure,which indicates its potential application in organic electronic devices.Solar cell devices that were fabricated using AFI as the electron acceptor and P3HT as the electron donor achieved an energy conversion efficiency of 0.33%.
基金supported by the National Basic Research Program of China (2013CB933701)the National Natural Science Foundation of China (81530009, 21127901, 91213305)Chinese Academy of Science
文摘Stimulation of G protein-coupled receptors(GPCRs) can lead to the transactivation of the epidermal growth factor receptors(EGFR). The cross-communication between the two signaling pathways regulates several important physiological or pathological processes. However, the molecule mechanism underlying EGFR transactivation remains poorly understood. Here, we aim to study the GPCR-mediated EGFR transactivation process using the single-molecule fluorescence imaging and tracking approach.We found that although EGFR existed as monomers at the plasma membrane of resting cells, they became dimers and thus diffused slower following the activation of β2-adrenergic receptor(β2-AR) by isoproterenol(ISO). We further proved thatβ2-AR-mediated changes of EGFR in stoichiometry and dynamics were mediated by Src kinase. Thus, the observations obtained via the single-molecule imaging and tracking methods shed new insights into the molecular mechanism of EGFR transactivation at single molecule level.
