共查询到20条相似文献,搜索用时 15 毫秒
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Kleppe R Martinez A Døskeland SO Haavik J 《Seminars in cell & developmental biology》2011,22(7):713-719
Thirty years ago, it was discovered that 14-3-3 proteins could activate enzymes involved in amino acid metabolism. In the following decades, 14-3-3s have been shown to be involved in many different signaling pathways that modulate cellular and whole body energy and nutrient homeostasis. Large scale screening for cellular binding partners of 14-3-3 has identified numerous proteins that participate in regulation of metabolic pathways, although only a minority of these targets have yet been subject to detailed studies. Because of the wide distribution of potential 14-3-3 targets and the resurging interest in metabolic pathway control in diseases like cancer, diabetes, obesity and cardiovascular disease, we review the role of 14-3-3 proteins in the regulation of core and specialized cellular metabolic functions. We cite illustrative examples of 14-3-3 action through their direct modulation of individual enzymes and through regulation of master switches in cellular pathways, such as insulin signaling, mTOR- and AMP dependent kinase signaling pathways, as well as regulation of autophagy. We further illustrate the quantitative impact of 14-3-3 association on signal response at the target protein level and we discuss implications of recent findings showing 14-3-3 protein membrane binding of target proteins. 相似文献
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14-3-3 proteins find new partners in plant cell signalling 总被引:1,自引:0,他引:1
Roberts MR 《Trends in plant science》2003,8(5):218-223
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BACKGROUND AND AIMS Mineral nutrient deficiencies and salinity constitute major limitations for crop plant growth on agricultural soils. 14-3-3 proteins are phosphoserine-binding proteins that regulate the activities of a wide array of targets via direct protein-protein interactions and may play an important role in responses to mineral nutrients deficiencies and salt stress. In the present study, the expression profiling of the 14-3-3 gene family in response to salt stress and potassium and iron deficiencies in young tomato (Solanum lycopersicum) roots was investigated in order to analyse the 14-3-3 roles of the proteins in these abiotic stresses. METHODS: Sequence identities and phylogenetic tree creation were performed using DNAMAN version 4.0 (Lynnon Biosoft Company). Real-time RT-PCR was used to examine the expression of each 14-3-3 gene in response to salt stress and potassium and iron deficiencies in young tomato roots. KEY RESULTS: The phylogenetic tree shows that the 14-3-3 gene family falls into two major groups in tomato plants. By using real-time RT-PCR, it was found that (a) under normal growth conditions, there were significant differences in the mRNA levels of 14-3-3 gene family members in young tomato roots and (b) 14-3-3 proteins exhibited diverse patterns of gene expression in response to salt stress and potassium and iron deficiencies in tomato roots. CONCLUSIONS: The results suggest that (a) 14-3-3 proteins may be involved in the salt stress and potassium and iron deficiency signalling pathways in young tomato roots, (b) the expression pattern of 14-3-3 gene family members in tomato roots is not strictly related to the position of the corresponding proteins within a phylogenetic tree, (c) gene-specific expression patterns indicate that isoform-specificity may exist in the 14-3-3 gene family of tomato roots, and (d) 14-3-3 proteins (TFT7) might mediate cross-talk between the salt stress and potassium and iron-deficiency signalling pathways in tomato roots. 相似文献
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The 14-3-3 proteins are binding proteins that have been shown to interact with a wide array of enzymes involved in primary biosynthetic and energy metabolism in plants. In most cases, the significance of binding of the 14-3-3 protein is not known. However, most of the interactions are phosphorylation-dependent and most of the known binding partners are found in the cytosol, while some may also be localized to plastids and mitochondria. In this review, we examine the factors that may regulate the binding of 14-3-3s to their target proteins, and discuss their possible roles in the regulation of the activity and proteolytic degradation of enzymes involved in primary carbon and nitrogen metabolism. 相似文献
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The 14-3-3 proteins are a family of highly conserved proteins found in all eukaryotes - from the yeasts to mammals. They regulate several cellular processes recognizing unique conservative, mostly phosphorylated motif of partner proteins. Binding of the 14-3-3 proteins regulates their partners through a variety of mechanisms, such as altering their catalytic activity, subcellular localization, stability or altering their interactions with other protein molecules. The native 14-3-3 proteins are present in form of homo- and hetero-dimers. The most structurally variable N-and C-termini are responsible for isoform specific protein-protein interactions, and cellular localization. In plant cell, 14-3-3 proteins appear to play an important role in regulation of key enzymes of carbon and nitrogen metabolism, modulation ion pumps and channels. They are also involved in signal transduction pathways and even in gene expression. 相似文献
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Pauly B Stiening B Schade M Alexandrova O Zoubek R David CN Böttger A 《Experimental cell research》2003,285(1):15-26
In the simple metazoan Hydra a clear link between food supply and cell survival has been established. Whilst in plants 14-3-3 proteins are found to be involved in signalling cascades that regulate metabolism, in animals they have been shown to participate in cell survival pathways. In order to explore the possibility that 14-3-3 proteins in Hydra could be involved in regulating metabolism under different conditions of food supply, we have cloned two isoforms of 14-3-3 proteins. We show here that 14-3-3 proteins bind to phosphorylated targets in Hydra and form homo- and heterodimers in vitro. 14-3-3 proteins are localised in the cytoplasm of all cells and also in the nuclei of some epithelial cells. This nuclear localisation becomes more prominent during starvation. Moreover, 14-3-3 protein is present in large amounts in food granules and from this we conclude that it performs functions which are associated with metabolism and food storage in Hydra. 相似文献
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Wang AH Kruhlak MJ Wu J Bertos NR Vezmar M Posner BI Bazett-Jones DP Yang XJ 《Molecular and cellular biology》2000,20(18):6904-6912
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Phosphorylation-dependent interactions between enzymes of plant metabolism and 14-3-3 proteins 总被引:20,自引:4,他引:16
Greg Moorhead Pauline Douglas Valérie Cotelle Jean Harthill Nick Morrice Sarah Meek Uta Deiting Mark Stitt Marie Scarabel Alastair Aitken Carol MacKintosh 《The Plant journal : for cell and molecular biology》1999,18(1):1-12
Far-Western overlays of soluble extracts of cauliflower revealed many proteins that bound to digoxygenin (DIG)-labelled 14-3-3 proteins. Binding to DIG-14-3-3s was prevented by prior dephosphorylation of the extract proteins or by competition with 14-3-3-binding phosphopeptides, indicating that the 14-3-3 proteins bind to phosphorylated sites. The proteins that bound to the DIG-14-3-3s were also immunoprecipitated from extracts with anti-14-3-3 antibodies, demonstrating that they were bound to endogenous plant 14-3-3 proteins. 14-3-3-binding proteins were purified from cauliflower extracts, in sufficient quantity for amino acid sequence analysis, by affinity chromatography on immobilised 14-3-3 proteins and specific elution with a 14-3-3-binding phosphopeptide. Purified 14-3-3-binding proteins included sucrose–phosphate synthase, trehalose-6-phosphate synthase, glutamine synthetases, a protein (LIM17) that has been implicated in early floral development, an approximately 20 kDa protein whose mRNA is induced by NaCl, and a calcium-dependent protein kinase that was capable of phosphorylating and rendering nitrate reductase (NR) sensitive to inhibition by 14-3-3 proteins. In contrast to the phosphorylated NR-14-3-3 complex which is activated by dissociation with 14-3-3-binding phosphopeptides, the total sugar–phosphate synthase activity in plant extracts was inhibited by up to 40% by a 14-3-3-binding phosphopeptide and the phosphopeptide-inhibited activity was reactivated by adding excess 14-3-3 proteins. Thus, 14-3-3 proteins are implicated in regulating several aspects of primary N and C metabolism. The procedures described here will be valuable for determining how the phosphorylation and 14-3-3-binding status of defined target proteins change in response to extracellular stimuli. 相似文献
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The 14-3-3 proteins, a family of conserved regulatory molecules, participate in a wide range of cellular processes through binding interactions with hundreds of structurally and functionally diverse proteins. Several distinct mechanisms of the 14-3-3 protein function were described, including conformational modulation of the bound protein, masking of its sequence-specific or structural features, and scaffolding that facilitates interaction between two simultaneously bound proteins. Details of these functional modes, especially from the structural point of view, still remain mostly elusive. This review gives an overview of the current knowledge concerning the structure of 14-3-3 proteins and their complexes as well as the insights it provides into the mechanisms of their functions. We discuss structural basis of target recognition by 14-3-3 proteins, common structural features of their complexes and known mechanisms of 14-3-3 protein-dependent regulations. 相似文献
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14-3-3 proteins are important eukaryotic regulatory proteins. Barley (Hordeum vulgare L.) 14-3-3A was over-expressed, immobilised and used to affinity purify 14-3-3 binding proteins from developing barley grains. Binding was shown to be phosphorylation-dependent. These proteins were fractionated by PAGE and identified by MALDI-TOF MS. In total, 54 14-3-3 binding proteins were identified, 49 of these interactions are novel to plants. These proteins fell into a number of functional categories. The largest category was for carbohydrate metabolism, including plastidic enzymes for starch synthesis and modification. 14-3-3 was shown to be present in isolated plastids. Four of five enzymes involved in sucrose biosynthesis from triose phosphates were identified, suggesting co-ordinated regulation of this pathway. Invertase and sucrose synthase, which break down sucrose to hexoses, were found. Sucrose synthase activity was shown to be inhibited by exogenous 14-3-3 in a dosage-dependent manner. The second-largest functional group was for proteins involved in stress and defence responses; for example, RGH2A, closely related to the MLA powdery mildew resistance protein, was found. This work illustrates the broad range of processes in which 14-3-3 may be involved, and augments previous data demonstrating key roles in carbohydrate metabolism and plant defence. 相似文献
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14-3-3 proteins regulate cellular responses to stimuli by docking onto pairs of phosphorylated residues on target proteins. The present study shows that the human 14-3-3-binding phosphoproteome is highly enriched in 2R-ohnologues, which are proteins in families of two to four members that were generated by two rounds of whole genome duplication at the origin of the vertebrates. We identify 2R-ohnologue families whose members share a 'lynchpin', defined as a 14-3-3-binding phosphosite that is conserved across members of a given family, and aligns with a Ser/Thr residue in pro-orthologues from the invertebrate chordates. For example, the human receptor expression enhancing protein (REEP) 1-4 family has the commonest type of lynchpin motif in current datasets, with a phosphorylatable serine in the -2 position relative to the 14-3-3-binding phosphosite. In contrast, the second 14-3-3-binding sites of REEPs 1-4 differ and are phosphorylated by different kinases, and hence the REEPs display different affinities for 14-3-3 dimers. We suggest a conceptual model for intracellular regulation involving protein families whose evolution into signal multiplexing systems was facilitated by 14-3-3 dimer binding to lynchpins, which gave freedom for other regulatory sites to evolve. While increased signalling complexity was needed for vertebrate life, these systems also generate vulnerability to genetic disorders. 相似文献
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Park DJ Freitas TA Wallick CJ Guyette CV Warn-Cramer BJ 《Protein science : a publication of the Protein Society》2006,15(10):2344-2355
The interaction of cellular proteins with the gap junction protein Connexin43 (Cx43) is thought to form a dynamic scaffolding complex that functions as a platform for the assembly of signaling, structural, and cytoskeletal proteins. A high stringency Scansite search of rat Cx43 identified the motif containing Ser373 (S373) as a 14-3-3 binding site. The S373 motif and the second best mode-1 motif, containing Ser244 (S244), are conserved in rat, mouse, human, chicken, and bovine, but not in Xenopus or zebrafish Cx43. Docking studies of a mouse/rat 14-3-3 homology model with the modeled phosphorylated S373 or S244 peptide ligands or their serine-to-alanine mutants, S373A or S244A, revealed that the pS373 motif facilitated a greater number of intermolecular contacts than the pS244 motif, thus supporting a stronger 14-3-3 binding interaction with the pS373 motif. The alanine substitution also reduced more than half the number of intermolecular contacts between 14-3-3 and the S373 motif, emphasizing the phosphorylation dependence of this interaction. Furthermore, the ability of the wild-type or the S244A GST-Cx43 C-terminal fusion protein, but not the S373A fusion protein, to interact with either 14-3-3 or 14-3-3zeta in GST pull-down experiments clearly demonstrated that the S373 motif mediates the direct interaction between Cx43 and 14-3-3 proteins. Blocking growth factor-induced Akt activation and presumably any Akt-mediated phosphorylation of the S373 motif in ROSE 199 cells did not prevent the down-regulation of Cx43-mediated cell-cell communication, suggesting that an Akt-mediated interaction with 14-3-3 was not involved in the disruption of Cx43 function. 相似文献
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The 14-3-3s are a group of proteins that are ubiquitously found in eukaryotes. Plant 14-3-3 proteins are encoded by a large
multigene family and are involved in signaling pathways to regulate plant development and protection from stress. Recent studies
in Arabidopsis and rice have demonstrated the isoform specificity in 14-3-3s and their client protein interactions. However, detailed characterization
of 14-3-3 gene family in legumes has not been reported. In this study, soybean 14-3-3 proteins were identified and their molecular
characterization performed. Data mining of soybean genome and expressed sequence tag databases identified 18 14-3-3 genes,
of them 16 are transcribed. All 16 SGF14s have higher expression in embryo tissues suggesting their potential role in seed development. Subcellular localization of
all transcribed SGF14s demonstrated that 14-3-3 proteins in soybean have isoform specificity, however, some overlaps were
also observed between closely related isoforms. A comparative analysis of SGF14s with Arabidopsis and rice 14-3-3s indicated that SGF14s also group into epsilon and non-epsilon classes. However, unlike Arabidopsis and rice 14-3-3s, SGF14s contained only one kind of gene structure belonging to each class. Overall, soybean consists of
the largest family of 14-3-3 proteins characterized to date. Our results provide a solid framework for further investigations
into the role of SGF14s and their involvement in legume-specific functions. 相似文献
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14-3-3 proteins and plant development 总被引:5,自引:0,他引:5
Fulgosi H Soll J de Faria Maraschin S Korthout HA Wang M Testerink C 《Plant molecular biology》2002,50(6):1019-1029
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14-3-3 proteins regulate the cell division cycle and play a pivotal role in blocking cell cycle advancement after activation of the DNA replication and DNA damage checkpoints. Here we describe a global proteomics analysis to identify proteins that bind to 14-3-3s during interphase and mitosis. 14-3-3-binding proteins were purified from extracts of interphase and mitotic HeLa cells using specific peptide elution from 14-3-3 zeta affinity columns. Proteins that specifically bound and eluted from the affinity columns were identified by microcapillary high pressure liquid chromatography tandem mass spectrometry analysis. Several known and novel 14-3-3-interacting proteins were identified in this screen. Identified proteins are involved in cell cycle regulation, signaling, metabolism, protein synthesis, nucleic acid binding, chromatin structure, protein folding, proteolysis, nucleolar function, and nuclear transport as well as several other cellular processes. In some cases 14-3-3 binding was cell cycle-dependent, whereas in other cases the binding was shown to be cell cycle-independent. This study adds to the growing list of human 14-3-3-binding proteins and implicates a role for 14-3-3 proteins in a plethora of essential biological processes. 相似文献
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14-3-3 Proteins are found to bind to a growing number of eukaryotic proteins and evidence is accumulating that 14-3-3 proteins serve as modulators of enzyme activity. Several 14-3-3 protein recognition motifs have been identified and an increasing number of target proteins have been found to contain more than one binding site for a 14-3-3 protein. It is thus possible that 14-3-3 dimers function as clamps that simultaneously bind to two motifs within a single binding partner. Phosphorylation of a number of binding motifs has been shown to increase the affinity for 14-3-3 proteins but other mechanisms also regulate the association. It has recently been demonstrated that fusicoccin induces a tight association between 14-3-3 proteins and the plant plasma membrane H+-ATPase. Phorbol esters and other hydrophobic molecules may have a similar effect on the association between 14-3-3 proteins and specific binding partners. 相似文献