共查询到20条相似文献，搜索用时 15 毫秒
1.
Perry SJ Baillie GS Kohout TA McPhee I Magiera MM Ang KL Miller WE McLean AJ Conti M Houslay MD Lefkowitz RJ 《Science (New York, N.Y.)》2002,298(5594):834-836
Catecholamines signal through the beta2-adrenergic receptor by promoting production of the second messenger adenosine 3',5'-monophosphate (cAMP). The magnitude of this signal is restricted by desensitization of the receptors through their binding to beta-arrestins and by cAMP degradation by phosphodiesterase (PDE) enzymes. We show that beta-arrestins coordinate both processes by recruiting PDEs to activated beta2-adrenergic receptors in the plasma membrane of mammalian cells. In doing so, the beta-arrestins limit activation of membrane-associated cAMP-activated protein kinase by simultaneously slowing the rate of cAMP production through receptor desensitization and increasing the rate of its degradation at the membrane. 相似文献
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Kovacs JJ Whalen EJ Liu R Xiao K Kim J Chen M Wang J Chen W Lefkowitz RJ 《Science (New York, N.Y.)》2008,320(5884):1777-1781
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To resolve the controversy about messengers regulating KCNQ ion channels during phospholipase C-mediated suppression of current, we designed translocatable enzymes that quickly alter the phosphoinositide composition of the plasma membrane after application of a chemical cue. The KCNQ current falls rapidly to zero when phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2 or PI(4,5)P2] is depleted without changing Ca2+, diacylglycerol, or inositol 1,4,5-trisphosphate. Current rises by 30% when PI(4,5)P2 is overproduced and does not change when phosphatidylinositol 3,4,5-trisphosphate is raised. Hence, the depletion of PI(4,5)P2 suffices to suppress current fully, and other second messengers are not needed. Our approach is ideally suited to study biological signaling networks involving membrane phosphoinositides. 相似文献
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Transduction of receptor signals by beta-arrestins 总被引：2，自引：0，他引：2
The transmission of extracellular signals to the interior of the cell is a function of plasma membrane receptors, of which the seven transmembrane receptor family is by far the largest and most versatile. Classically, these receptors stimulate heterotrimeric G proteins, which control rates of generation of diffusible second messengers and entry of ions at the plasma membrane. Recent evidence, however, indicates another previously unappreciated strategy used by the receptors to regulate intracellular signaling pathways. They direct the recruitment, activation, and scaffolding of cytoplasmic signaling complexes via two multifunctional adaptor and transducer molecules, beta-arrestins 1 and 2. This mechanism regulates aspects of cell motility, chemotaxis, apoptosis, and likely other cellular functions through a rapidly expanding list of signaling pathways. 相似文献
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Glycosylphosphatidylinositol: a candidate system for interleukin-2 signal transduction 总被引：12，自引：0，他引：12
The mechanism of interleukin-2 (IL-2) signal transduction was analyzed by use of an inducible B lymphoma. Like normal antigen-activated B lymphocytes, the lymphoma cells respond to IL-2 by proliferating and differentiating into antibody-secreting cells; both responses are blocked by a second interleukin, IL-4. Analyses of the signaling pathway showed that IL-2 stimulated the rapid hydrolysis of an inositol-containing glycolipid to yield two possible second messengers, a myristylated diacylglycerol and an inositol phosphate-glycan. The myristylated diacylglycerol response exhibited the same IL-2 dose dependence as the growth and differentiative responses, and the generation of both hydrolysis products was inhibited by IL-4. These correlations implicate the glycosyl-phosphatidylinositol system in the intracellular relay of the IL-2 signal. 相似文献
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为掌握微生物降解甲基毒死蜱的特性与机制,首先从土壤中分离不同的甲基毒死蜱降解茵,然后对其降解效率、降解过程中中间产物3,5,6-三氯-2-吡啶酚(TCP)的质量浓度变化、对TCP与其他6种有机磷农药的降解能力以及磷酸酯酶活性进行了测试分析.结果表明,分离到2株能高效降解甲基毒死蜱的菌株,经鉴定命名为地衣芽孢杆菌ZL-7与荧光假单胞茵ZHLXL-2,其降解甲基毒死蜱的5d降解率分别为90.6％和99.4％;在菌株ZL-7降解甲基毒死蜱的过程中检出了TCP,而在菌株ZHLXL-2的降解过程中未检出.菌株ZHLXL-2能降解TCP,48 h降解率可达91.0％,而菌株ZL-7不能降解TCP.两菌株都能降解6种供试的有机磷农药,但菌株ZL-7降解率更高,其10 d降解率在92.1％ ～99.8％,菌株ZHLXL-2的10 d降解率为89.2％～93.4％;同时菌株ZL-7的磷酸酯酶活性显著高于菌株ZHLXL-2.分析表明,这2种菌株的磷酸酯酶活性与其降解有机磷农药的能力呈正相关性,而菌株ZHLXL-2因可有效降解中间物TCP,从而能更快地降解甲基毒死蜱. 相似文献
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Chen W Kirkbride KC How T Nelson CD Mo J Frederick JP Wang XF Lefkowitz RJ Blobe GC 《Science (New York, N.Y.)》2003,301(5638):1394-1397
beta-Arrestins bind to activated seven transmembrane-spanning (7TMS) receptors (G protein-coupled receptors) after the receptors are phosphorylated by G protein-coupled receptor kinases (GRKs), thereby regulating their signaling and internalization. Here, we demonstrate an unexpected and analogous role of beta-arrestin 2 (betaarr2) for the single transmembrane-spanning type III transforming growth factor-beta (TGF-beta) receptor (TbetaRIII, also referred to as betaglycan). Binding of betaarr2 to TbetaRIII was also triggered by phosphorylation of the receptor on its cytoplasmic domain (likely at threonine 841). However, such phosphorylation was mediated by the type II TGF-beta receptor (TbetaRII), which is itself a kinase, rather than by a GRK. Association with betaarr2 led to internalization of both receptors and down-regulation of TGF-beta signaling. Thus, the regulatory actions of beta-arrestins are broader than previously appreciated, extending to the TGF-beta receptor family as well. 相似文献
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Assemblage of ortho cleavage route for simultaneous degradation of chloro- and methylaromatics 总被引：24，自引：0，他引：24
F Rojo D H Pieper K H Engesser H J Knackmuss K N Timmis 《Science (New York, N.Y.)》1987,238(4832):1395-1398
Genetic engineering is a powerful means of accelerating the evolution of new biological activities and has considerable potential for constructing microorganisms that can degrade environmental pollutants. Critical enzymes from five different catabolic pathways of three distinct soil bacteria have been combined in patchwork fashion into a functional ortho cleavage route for the degradation of methylphenols and methylbenzoates. The new bacterium thereby evolved was able to degrade and grow on mixtures of chloro- and methylaromatics that were toxic even for the bacteria that could degrade the individual components of the mixtures. Except for one enzymatic step, the pathway was fully regulated and its component enzymes were only synthesized in response to the presence of pathway substrates. 相似文献
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Estrogen-induced factors of breast cancer cells partially replace estrogen to promote tumor growth 总被引：12，自引：0，他引：12
The hormone 17 beta-estradiol acts through its receptor system to induce MCF-7 human breast cancer cells to form tumors in athymic mice. In vitro studies have identified the production of estrogen-induced growth factors from MCF-7 cells that may have a role in growth control. These induced growth factors were sufficient to stimulate MCF-7 tumor growth in ovariectomized athymic mice, thus partially replacing estradiol. Growth factors may act as estrogen-induced "second messengers" in estrogen-responsive growth of human breast cancer. 相似文献
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多效唑对绿豆黄化幼苗生长及肌醇磷脂代谢的抑制作用 总被引：5，自引：0，他引：5
多效唑抑制绿豆黄化幼苗生长和茎尖初生分生组织细胞分裂,降低内源ＩＡＡ、ＡＢＡ和甾醇水平。应用放射性标记及薄层层析技术,发现多效唑抑制肌醇磷脂代谢,ＰＩ、ＰＩＰ和ＰＩＰ２含量均高于对照,而ＤＡＧ含量低于对照。 相似文献
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Early signal transduction by the antigen receptor without commitment to T cell activation 总被引：18，自引：0，他引：18
The T lymphocyte antigen-receptor complex mediates antigen-specific cell activation, at least in part, through the production of inositolphospholipid-derived second messengers. Little is known about how second messenger events, typically measured within minutes of ligand binding, eventually lead to distal biologic responses such as expression of lymphokine genes. Several monoclonal antibodies directed against the receptor complex were tested for their ability to elicit transmembrane signaling in the parental Jurkat line and in a somatic mutant (J.CaM1) with a deficient receptor function. One antibody elicited substantial early Ca2+ mobilization responses in both cells but was unable to promote expression of the interleukin-2 gene in J.CaM1. In J.CaM1 there was a diminished production of phosphatidylinositol second messengers, and the elevation in intracellular free Ca2+ was transient. Thus, short-term Ca2+ mobilization does not always indicate complete signal transmission and lead to a full cellular response. 相似文献
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甲基对硫磷水解酶(MPH)能高效降解甲基对硫磷,并能够降解杀螟松、乙基对硫磷和毒死蜱,但降解效率依次降低。为提高MPH对毒死蜱的降解活性,采用易错PCR的方法对MPH进行随机突变,筛选到2株突变体A291V和K173R,并对其进行原核表达,结果表明K173R对毒死蜱的降解活性比MPH提高了41.55%。通过同源建模及与毒死蜱的分子对接对酶的结构和功能进行初步分析,结果发现氨基酸残基R72在酶与毒死蜱的结合中起着重要作用。结合口袋和关键氨基酸的变化可最终导致K173R酶活性的提高。 相似文献
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Cyclosporin A, a potent immunosuppressive agent, has been widely used to treat patients with solid organ transplants. Although its precise mechanism of action is unknown, it appears to inhibit subsets of T lymphocytes at an early stage in cell activation. Fluorescent, fully active derivatives of cyclosporin A and calmodulin, a protein that binds calcium and is therefore essential to normal cell function, were utilized to demonstrate that cyclosporin A binds to calmodulin. Flow cytometry showed that the calmodulin inhibitors R24571 and W-7 competitively inhibited binding of cyclosporin A to cloned T lymphocytes. Cyclosporin A inhibited the calmodulin-dependent activation of phosphodiesterase in a dose-dependent manner. Binding of cyclosporin A to calmodulin may prevent the latter's role in the activation of the second messengers and enzymes required for effective cell proliferation and function in the immune response. 相似文献
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Activity-dependent plasticity in the brain arises in part from changes in the number of synaptic AMPA receptors. Synaptic trafficking of AMPA receptors is controlled by stargazin and homologous transmembrane AMPA receptor regulatory proteins (TARPs). We found that TARPs were stable at the plasma membrane, whereas AMPA receptors were internalized in a glutamate-regulated manner. Interaction with AMPA receptors involved both extra- and intracellular determinants of TARPs. Upon binding to glutamate, AMPA receptors detached from TARPs. This did not require ion flux or intracellular second messengers. This allosteric mechanism for AMPA receptor dissociation from TARPs may participate in glutamate-mediated internalization of receptors in synaptic plasticity. 相似文献
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Gary E Harmant James Lynch Matteo Lorito 《浙江大学学报(农业与生命科学版)》2004,30(4):440-440
Trichoderma spp. probably have a role in remediation of polluted soils and waters. Highly rhizosphere competent strains persist on roots for an extended period of time (at least months) and continuously interact with the plants. They can increase general plant and root growth and increase uptake of a variety of materials. This makes the Trichoderma-plant interaction highly attractive for use in phytoextraction technologies. Moreover, Trichoderma spp. are resistant to a wide range of toxic… 相似文献
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microRNAs (miRNAs) play crucial roles in numerous developmental and metabolic processes in plants and animals. The steady-state levels of miRNAs need to be properly controlled to ensure normal development. Whereas the framework of miRNA biogenesis is established, factors involved in miRNA degradation remain unknown. Here, we show that a family of exoribonucleases encoded by the SMALL RNA DEGRADING NUCLEASE (SDN) genes degrades mature miRNAs in Arabidopsis. SDN1 acts specifically on single-stranded miRNAs in vitro and is sensitive to the 2'-O-methyl modification on the 3' terminal ribose of miRNAs. Simultaneous knockdown of three SDN genes in vivo results in elevated miRNA levels and pleiotropic developmental defects. Therefore, we have uncovered the enzymes that degrade miRNAs and demonstrated that miRNA turnover is crucial for plant development. 相似文献
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用木瓜蛋白酶、胰蛋白酶和A s1.398枯草蛋白酶分别对豆粕、棉粕、菜粕和花生粕的蛋白质进行酶解,并对其酶解产物进行超滤分析及用产物对小鼠胚胎成纤维细胞进行培养试验,探讨不同蛋白酶解产物的蛋白质组成及对细胞生长的影响。结果表明:酶解产物中蛋白质分子质量分布与酶的种类和植物蛋白质种类有关,其中A s1.398枯草蛋白酶对豆粕酶解能力最强,酶解产物中蛋白质分子质量小于3 ku的比例占31.67%;各酶解产物对小鼠胚胎成纤维细胞生长都有促进作用,以A s1.398枯草蛋白酶酶解的棉粕产物对小鼠胚胎成纤维细胞生长的促进作用最好,其细胞生长速度比豆粕、菜粕和花生粕酶解产物组显著提高。 相似文献