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1.
G蛋白信号通路是细胞跨膜信号转导体系中的重要组成部分,其转导信号的功能涉及广泛的细胞生物学活动。G蛋白的信号转导特性与结合GTP的α亚单位和βγ亚单位异二聚体有关。越来越多的研究表明,βγ亚单位在维持信号转导的保真度和信号转导途径交联中扮演着关键角色。 相似文献
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G蛋白亚单位基因家族研究进展 总被引:3,自引:0,他引:3
G蛋白由α、β、γ三个亚单位组成异源三聚体。目前已发现16个α、6个β和12个γ基因。G蛋白亚单位基因家族相当保守并且原始,几乎所有G蛋白基因外显子-内含子连接均遵从GT-AG规则,并且各亚单位基因编码区内含子结构和位置显示出很高的保守性。多数G蛋白基因具有持家基因的特点。G蛋白基因在基因组中的分布存在着丛集的倾向,有5对α基因呈二联串连排列。 相似文献
3.
G蛋白偶联受体激酶(G protein-coupled receptor kinase,GRK)特异地使活化的G蛋白偶联受体(G protein-coupled receptor,GPCR)发生磷酸化及脱敏化,从而终止后者介导的信号转导通路。研究表明,GRK的功能被高度调控,并具有下行调节GPCR的能力。调控GRK功能的机制包括两个层次:(1)多种途径调控激酶的亚细胞定位及活性,包括GPCR介导、G蛋白偶联、磷脂作用、Ca^2 结合蛋白调控、蛋白激酶C活化、MAPK反馈抑制、小窝蛋白抑制等;(2)调控GRK表达水平,主要体现在其与某些疾病的联系。 相似文献
4.
近年来发现一些G蛋白偶联受体(GPCR)能在细胞膜上形成同源或异源双聚体,并证实受体的双聚化为一些有重要生理功能的GPCR在细胞膜上的表达和信号转导的启动所必需,进一步研究表明,一些GPCR的双聚化不仅可以改变受体与配体结合的特异性和亲和力,而且影响GPCR介导的信号转导的调控,这些结果提示,GPCR之间以及GPCR与其它蛋白在细胞膜上的相互作用是调控GPCR转导信号的一个新途径。 相似文献
5.
G—蛋白及其在植物信号转导中的作用 总被引:3,自引:0,他引:3
GTP结合蛋白(GTP-bindingprotein)在生物体内有数种类型,包括转录因子、微管蛋白和信号转导蛋白,最后一种已成为当今研究的热点。结合GTP的调节蛋白(GTP-bindingregulatoryproteins,简称G-蛋白)于70年代... 相似文献
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Methuselah(MTH)是果蝇来源的GPCR中的一员,它的突变可延长果蝇平均寿命并提高果蝇对外界胁迫因素的耐受性。但目前对MTH在细胞水平的信号转导研究鲜有报道。该研究用稳定表达MTH的HEK293细胞株,对与该受体偶联的G蛋白选择性做了研究。首先,用免疫荧光染色、Western blot及钙流实验验证了MTH在HEK293/Myc-MTH细胞表面能稳定表达,且具有正常生物学活性;MTH受体被其配体N-stunted活化后所引起细胞内钙的上升不能被PTX预处理抑制,提示活化的MTH可能通过与Gq/11而非Gi/o蛋白相偶联;进一步研究发现,MTH激活后不显著改变细胞中的cAMP水平,表明MTH不与Gs和Gi/o相偶联;MTH被激活后可引起ERK磷酸化。这些结果提示:MTH可能是Gq/11蛋白的偶联受体,为进一步研究MTH的下游信号转导和生物学功能奠定了基础。 相似文献
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AGS3蛋白是影响受体到G蛋白的信号转导或直接影响非受体依赖型G蛋白激活的蛋白质之一。AGS3蛋白在脑、睾丸、肝脏、肾脏、心脏、胰腺及PC-12细胞中普遍分布。它不仅具有不依赖受体的Gβγ信号转导激活物的作用,也能作为二磷酸乌苷(GDP)的解离抑制剂,并负向调节G蛋白偶联受体对G蛋白的激活。AGSl、AGS2、AGS4是AGS家族的其它几个成员,能选择性激活不同类型的G蛋白。LGN和PINS蛋白是AGS3的同系物。AGS3蛋白与信号转导的关系是目前研究的热点之一。 相似文献
10.
脱落酸(ABA)是一种重要的植物激素,参与了种子萌发、气孔关闭及植物抗逆等多种生理过程。最新研究鉴定了ABA的三种类型受体,即FCA、CHLH和GCR2,特别是GCR2介导的信号转导(包括G蛋白偶联受体、G蛋白、相关靶酶等)研究取得重大突破,使人们对ABA的作用机制有了全面理解,从而为农业应用奠定了坚实基础。 相似文献
11.
Heterotrimeric G protein signaling is involved in many pathways essential to development including those controlling cell migration, proliferation, differentiation and apoptosis. One key developmental event known to rely on proper heterotrimeric G protein signaling is primordial germ cell (PGC) migration. We previously developed an in vivo PGC migration assay that identified differences in the signaling capacity of G protein gamma subunits. In this study we developed Gγ subunit chimeras to determine the regions of Gγ isoforms that are responsible for these differences. The central section of the Gγ subunit was found to be necessary for the ability of a Gγ subunit to mediate signaling involved in PGC migration. Residues found in the carboxy-terminal segment of Gγ transducin (gngt1) were found to be responsible for the ability of this subunit to disrupt PGC migration. The type of prenylation did not affect the ability of a Gγ subunit to reverse prenylation-deficient-Gγ-induced PGC migration defects. However, a version of gng2, engineered to be farnesylated instead of geranylgeranylated, still lacks the ability to reverse PGC migration defects known to result from treatment of zebrafish with geranylgeranyl transferase inhibitors (GGTI), supporting the notion that Gγ subunits are one of several protein targets that need to be geranylgeranylated to orchestrate the proper long-range migration of PGCs. 相似文献
12.
The complex role that the heterotrimeric G proteins play in signaling pathways has become increasingly apparent with the cloning of countless numbers of receptors, G proteins, and effectors. However, in most cases, the specific combinations of alpha and betagamma subunits comprising the G proteins that participate in the most common signaling pathways, such as beta-adrenergic regulation of adenylyl cyclase activity, are not known. The extent of this problem is evident in the fact that the identities of the betagamma subunits that combine with the alpha subunit of Gs are only now being elucidated almost 20 years after its initial purification. In a previous study, we described the first use of a ribozyme strategy to suppress specifically the expression of the gamma7 subunit of the G proteins, thereby identifying a specific role of this protein in coupling the beta-adrenergic receptor to stimulation of adenylyl cyclase activity in HEK 293 cells. In the present study, we explored the potential utility of a ribozyme approach directed against the gamma7 subunit to identify functional associations with a particular beta and alphas subunit of the G protein in this signaling pathway. Accordingly, HEK 293 cells were transfected with a ribozyme directed against the gamma7 subunit, and the effects of this manipulation on levels of the beta and alphas subunits were determined by immunoblot analysis. Among the five beta alphas subunits detected in these cells, only the beta1 subunit was coordinately reduced following treatment with the ribozyme directed against the gamma7 subunit, thereby demonstrating a functional association between the beta1 and gamma7 subunits. The mechanism for coordinate suppression of the beta1 subunit was due to a striking change in the half-life of the beta1 monomer versus the beta1 heterodimer complexed with the gamma7 subunit. Neither the 52- nor 45-kDa subunits were suppressed following treatment with the ribozyme directed against the gamma7 subunit, thereby providing insights into the assembly of the Gs heterotrimer. Taken together, these data show the utility of a ribozyme approach to identify the role of not only the gamma subunits but also the beta subunits of the G proteins in signaling pathways. 相似文献
13.
Prenylation of G protein gamma (γ) subunits is necessary for the membrane localization of heterotrimeric G proteins and for functional heterotrimeric G protein coupled receptor (GPCR) signaling. To evaluate GPCR signaling pathways during development, we injected zebrafish embryos with mRNAs encoding Gγ subunits mutated so that they can no longer be prenylated. Low-level expression of these prenylation-deficient Gγ subunits driven either ubiquitously or specifically in the primordial germ cells (PGCs) disrupts GPCR signaling and manifests as a PGC migration defect. This disruption results in a reduction of calcium accumulation in the protrusions of migrating PGCs and a failure of PGCs to directionally migrate. When co-expressed with a prenylation-deficient Gγ, 8 of the 17 wildtype Gγ isoforms individually confer the ability to restore calcium accumulation and directional migration. These results suggest that while the Gγ subunits possess the ability to interact with G Beta (β) proteins, only a subset of wildtype Gγ proteins are stable within PGCs and can interact with key signaling components necessary for PGC migration. This in vivo study highlights the functional redundancy of these signaling components and demonstrates that prenylation-deficient Gγ subunits are an effective tool to investigate the roles of GPCR signaling events during vertebrate development. 相似文献
14.
Differential distribution of alpha subunits and beta gamma subunits of heterotrimeric G proteins on Golgi membranes of the exocrine pancreas 总被引:3,自引:0,他引:3
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《The Journal of cell biology》1996,133(5):1027-1040
Heterotrimeric G proteins are well known to be involved in signaling via plasma membrane (PM) receptors. Recent data indicate that heterotrimeric G proteins are also present on intracellular membranes and may regulate vesicular transport along the exocytic pathway. We have used subcellular fractionation and immunocytochemical localization to investigate the distribution of G alpha and G beta gamma subunits in the rat exocrine pancreas which is highly specialized for protein secretion. We show that G alpha s, G alpha i3 and G alpha q/11 are present in Golgi fractions which are > 95% devoid of PM. Removal of residual PM by absorption on wheat germ agglutinin (WGA) did not deplete G alpha subunits. G alpha s was largely restricted to TGN- enriched fractions by immunoblotting, whereas G alpha i3 and G alpha q/11 were broadly distributed across Golgi fractions. G alpha s did not colocalize with TGN38 or caveolin, suggesting that G alpha s is associated with a distinct population of membranes. G beta subunits were barely detectable in purified Golgi fractions. By immunofluorescence and immunogold labeling, G beta subunits were detected on PM but not on Golgi membranes, whereas G alpha s and G alpha i3 were readily detected on both Golgi and PM. G alpha and G beta subunits were not found on membranes of zymogen granules. These data indicate that G alpha s, G alpha q/11, and G alpha i3 associate with Golgi membranes independent of G beta subunits and have distinctive distributions within the Golgi stack. G beta subunits are thought to lock G alpha in the GDP-bound form, prevent it from activating its effector, and assist in anchoring it to the PM. Therefore the presence of free G alpha subunits on Golgi membranes has several important functional implications: it suggests that G alpha subunits associated with Golgi membranes are in the active, GTP-bound form or are bound to some other unidentified protein(s) which can substitute for G beta gamma subunits. It further implies that G alpha subunits are tethered to Golgi membranes by posttranslational modifications (e.g., palmitoylation) or by binding to another protein(s). 相似文献
15.
Different signaling and cell death roles of heterotrimeric G protein alpha and beta subunits in the Arabidopsis oxidative stress response to ozone 总被引:2,自引:0,他引:2
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Arabidopsis thaliana plants with null mutations in the genes encoding the alpha and beta subunits of the single heterotrimeric G protein are less and more sensitive, respectively, to O3 damage than wild-type Columbia-0 plants. The first peak of the bimodal oxidative burst elicited by O3 in wild-type plants is almost entirely missing in both mutants. The late peak is normal in plants lacking the Gbeta protein but missing in plants lacking the Galpha protein. Endogenous reactive oxygen species (ROS) are first detectable in chloroplasts of leaf epidermal guard cells. ROS production in adjacent cells is triggered by extracellular ROS signals produced by guard cell membrane-associated NADPH oxidases encoded by the AtrbohD and AtrbohF genes. The late, tissue damage-associated component of the oxidative burst requires only the Galpha protein and arises from multiple cellular sources. The early component of the oxidative burst, arising primarily from chloroplasts, requires signaling through the heterotrimer (or the Gbetagamma complex) and is separable from Galpha-mediated activation of membrane-bound NADPH oxidases necessary for both intercellular signaling and cell death. 相似文献
16.
Mirshahi T Mittal V Zhang H Linder ME Logothetis DE 《The Journal of biological chemistry》2002,277(39):36345-36350
G proteins interact with effectors at multiple sites and regulate their activity. The functional significance of multiple contact points is not well understood. We previously identified three residues on distinct surfaces of Gbetagamma that are crucial for G protein-coupled inward rectifier K(+) (GIRK) channel activation. Here we show that mutations at these sites, S67K, S98T, and T128F, abolished or reduced direct GIRK current activation in inside-out patches, but, surprisingly, all mutants synergized with sodium in activating K(+) currents. Each of the three Gbeta(1) mutants bound the channel indicating that the defects reflected mainly functional impairments. We tested these mutants for functional interactions with effectors other than K(+) channels. With N-type calcium channels, Gbetagamma wild type and mutants all inhibited basal currents. A depolarizing pre-pulse relieved Gbetagamma inhibition of Ca(2+) currents by the wild type and the S98T and T128F mutants but not the S67K mutant. Both wild type and mutant Gbetagamma subunits activated phospholipase C beta(2) with similar potencies; however, the S67K mutant showed reduced maximal activity. These data establish a pattern where mutations can alter the Gbetagamma regulation of a specific effector function without affecting other Gbetagamma-mediated functions. Moreover, Ser-67 showed this pattern in all three effectors tested, suggesting that this residue participates in a common functional domain on Gbeta(1) that regulates several effectors. These data show that distinct domains within Gbetagamma subserve specific functional roles. 相似文献
17.
Human phosphatidylethanolamine-binding protein facilitates heterotrimeric G protein-dependent signaling 总被引:1,自引:0,他引:1
In this study we report that human phosphatidylethanolamine-binding protein (hPBP) facilitates heterotrimeric G protein-coupled signaling. In Xenopus laevis oocytes, coexpression of hPBP with human mu opioid receptor, human delta opioid receptor, or human somatostatin receptor 2 evoked an agonist-induced increase in potassium conductance of G protein-activated inwardly rectifying potassium channels. This activation of heterotrimeric G protein signaling in oocytes could also be elicited by injection of bacterially overexpressed and purified hPBP. Stimulatory effect was pertussis toxin-sensitive and present even in the absence of coexpressed receptors. Additionally, an increase in G protein-mediated inhibition of adenylate cyclase activity, measured by the inhibition of forskolin-mediated cAMP accumulation, could be detected in HEK293 and NIH3T3 cells after expression of hPBP and in Xenopus oocytes after injection of hPBP. As [(35)S]guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding to membranes prepared from hPBP-expressing cells was significantly elevated and recombinant hPBP dose-dependently stimulated [(35)S]GTPgammaS binding to native membranes, the results presented provide strong evidence that hPBP-induced effects are G protein-dependent. These data suggest a novel function of hPBP in regulating G protein and G protein-coupled receptor signaling in vivo. 相似文献
18.
S Lotersztajn C Pavoine P Deterre J Capeau A Mallat D LeNguyen M Dufour B Rouot D Bataille F Pecker 《The Journal of biological chemistry》1992,267(4):2375-2379
In Zajdela hepatoma cells (ZHC) the plasma membrane Ca2+ pump displayed no sensitivity to glucagon (19-29) (mini-glucagon), whereas in hepatocyte this metabolite of glucagon evoked a biphasic regulation of the Ca2+ pump system via a cholera toxin-sensitive G protein. Analysis of G protein subunits in ZHC membranes indicated the presence of cholera toxin-sensitive Gs alpha and G beta gamma proteins, whose functionality was manifested by GTP and NaF stimulation of adenylylcyclase activity, and pertussis toxin-catalyzed ADP-ribosylation of Gi alpha, respectively. However, immunoblotting experiments suggested a lower content in beta gamma subunits in ZHC as compared with hepatocyte plasma membranes. Complementation of ZHC or hepatocyte plasma membranes with purified beta gamma subunits from transducin (T beta gamma) caused inhibition of the basal activity of the Ca2+ pump at 10 and 300 ng/ml, respectively, and revealed (in ZHC) or increased (in hepatocytes) sensitivity of the system to mini-glucagon. After cholera toxin treatment of ZHC, T beta gamma no longer reconstituted the response of the Ca2+ pump to mini-glucagon, suggesting that the mechanism of beta gamma action is dependent on an association with the alpha subunit of a cholera toxin-sensitive G protein. It is concluded that G beta gamma subunits control both the basal activity of the plasma membrane Ca2+ pump and its inhibition by mini-glucagon. 相似文献
19.
《遗传学报》2016,(8)
Heterotrimeric guanine nucleotide-binding protein(G protein) signaling is an evolutionary conserved mechanism in diverse eukaryotic organisms.In plants,the repertoire of the heterotrimeric G protein complex,which is composed of the Gα,Gβ,and Gγ subunits,is much simpler than that in metazoans,and the identity of typical G protein-coupled receptors(GPCRs) together with their ligands still remains unclear.Comparative phenotypic analysis in Arabidopsis and rice plants using gain- and loss-of-function mutants of G protein components revealed that heterotrimeric G protein signaling plays important roles in a wide variety of plant growth and developmental processes.Grain yield is a complex trait determined by quantitative trait loci(QTL) and is influenced by soil nitrogen availability and environmental changes.Recent studies have shown that the manipulation of two non-canonical Gy subunits,GS3(GRAIN SIZE 3)and DEP1(DENSE AND ERECT PANICLE 1),represents new strategies to simultaneously increase grain yield and nitrogen use efficiency in rice.This review discusses the latest advances in our understanding of the heterotrimeric G protein signal transduction pathway and its application in improving yield and stress tolerance in crops. 相似文献
20.
Trusov Y Rookes JE Tilbrook K Chakravorty D Mason MG Anderson D Chen JG Jones AM Botella JR 《The Plant cell》2007,19(4):1235-1250
The Arabidopsis thaliana heterotrimeric G protein complex is encoded by single canonical Galpha and Gbeta subunit genes and two Ggamma subunit genes (AGG1 and AGG2), raising the possibility that the two potential G protein complexes mediate different cellular processes. Mutants with reduced expression of one or both Ggamma genes revealed specialized roles for each Ggamma subunit. AGG1-deficient mutants, but not AGG2-deficient mutants, showed impaired resistance against necrotrophic pathogens, reduced induction of the plant defensin gene PDF1.2, and decreased sensitivity to methyl jasmonate. By contrast, both AGG1- and AGG2-deficient mutants were hypersensitive to auxin-mediated induction of lateral roots, suggesting that Gbetagamma1 and Gbetagamma2 synergistically inhibit auxin-dependent lateral root initiation. However, the involvement of each Ggamma subunit in this root response differs, with Gbetagamma1 acting within the central cylinder, attenuating acropetally transported auxin signaling, while Gbetagamma2 affects the action of basipetal auxin and graviresponsiveness within the epidermis and/or cortex. This selectivity also operates in the hypocotyl. Selectivity in Gbetagamma signaling was also found in other known AGB1-mediated pathways. agg1 mutants were hypersensitive to glucose and the osmotic agent mannitol during seed germination, while agg2 mutants were only affected by glucose. We show that both Ggamma subunits form functional Gbetagamma dimers and that each provides functional selectivity to the plant heterotrimeric G proteins, revealing a mechanism underlying the complexity of G protein-mediated signaling in plants. 相似文献