Target of Rapamycin

雷帕霉素靶点
  • 文章类型: Journal Article
    雷帕霉素(TOR)激酶的靶标充当整合营养和能量信号以协调动物和植物中的细胞和生物体生理学的中央调节剂。尽管在理解植物TOR激酶的分子和细胞功能方面取得了重大进展,调节TOR活性的上游调节因子尚未完全阐明.在动物中,翻译控制的肿瘤蛋白(TCTP)被认为是TOR信号传导的关键参与者。这项研究揭示了黄瓜的两种TCTP亚型,当被引入拟南芥时,有助于平衡针对真菌病原体菊苣的生长和防御机制。我们假设植物TCTP充当TOR的上游调节剂,以响应黄瓜中Podosphaeraxanthii引起的白粉病。我们的研究进一步揭示了CsTCTP和小GTP酶之间的稳定相互作用,CsRab11A.瞬时转化测定表明CsRab11A参与了对黄硫疟原虫的防御,并通过CsTCTP促进了TOR信号的激活。此外,我们的发现表明,TOR在植物抗病性中的关键作用取决于其调节的活性;用TOR抑制剂(AZD-8055)预处理可增强黄瓜植物对黄硫的抗性。而用TOR激活剂(MHY-1485)预处理会增加易感性。这些结果表明了一种复杂的自适应响应机制,其中上游监管机构,CsTCTP和CsRab11A,协调调节TOR功能,以响应黄氏疟原虫,突出了植物-病原体相互作用的一个新方面。
    The target of rapamycin (TOR) kinase serves as a central regulator that integrates nutrient and energy signals to orchestrate cellular and organismal physiology in both animals and plants. Despite significant advancements having been made in understanding the molecular and cellular functions of plant TOR kinases, the upstream regulators that modulate TOR activity are not yet fully elucidated. In animals, the translationally controlled tumor protein (TCTP) is recognized as a key player in TOR signaling. This study reveals that two TCTP isoforms from Cucumis sativus, when introduced into Arabidopsis, are instrumental in balancing growth and defense mechanisms against the fungal pathogen Golovinomyces cichoracearum. We hypothesize that plant TCTPs act as upstream regulators of TOR in response to powdery mildew caused by Podosphaera xanthii in Cucumis. Our research further uncovers a stable interaction between CsTCTP and a small GTPase, CsRab11A. Transient transformation assays indicate that CsRab11A is involved in the defense against P. xanthii and promotes the activation of TOR signaling through CsTCTP. Moreover, our findings demonstrate that the critical role of TOR in plant disease resistance is contingent upon its regulated activity; pretreatment with a TOR inhibitor (AZD-8055) enhances cucumber plant resistance to P. xanthii, while pretreatment with a TOR activator (MHY-1485) increases susceptibility. These results suggest a sophisticated adaptive response mechanism in which upstream regulators, CsTCTP and CsRab11A, coordinate to modulate TOR function in response to P. xanthii, highlighting a novel aspect of plant-pathogen interactions.
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  • 文章类型: Journal Article
    在皮氏,吸血螨,血液喂养引起的卵黄发生的启动对其繁殖至关重要。然而,Gallinae及其上游基因中Vg的精确基因结构和生理功能,雷帕霉素靶蛋白(TOR),还没有被完全理解。这项研究揭示了D.gallinae中存在四个同源基因,命名为Dg-Vg1,类似Dg-Vg1,Dg-Vg2,Dg-Vg2,尤其是,首先在螨虫中鉴定出Dg-Vg2样。所有这些Vg基因的表达水平在成年雌性中明显高于其他阶段。采血后,这些基因的表达水平显著增加,随后下降,与鸡蛋生产保持一致。通过RNA干扰(RNAi)沉默Dg-Vgs导致繁殖力和卵孵化率降低,以及异常的胚胎发育,提示Dg-Vgs在卵形成和胚胎发育中的重要作用。此外,Dg-TOR的敲减会显著降低Dg-Vgs的表达,并对PRM的繁殖能力产生负面影响,表明TOR通过调节Dg-Vgs的表达影响PRM繁殖。总之,这些发现证明了Dg-Vgs和Dg-TOR在PRM繁殖中的关键作用,强调它们作为虫害防治目标的潜力。
    In Dermanyssus gallinae, a hematophagous mite, the initiation of vitellogenesis induced by blood feeding is essential for its reproduction. However, the precise gene structures and physiological functions of Vg in D. gallinae and its upstream gene, Target of Rapamycin (TOR), have not been fully understood. This study revealed the presence of four homologous genes within D. gallinae, named Dg-Vg1, Dg-Vg1-like, Dg-Vg2, and Dg-Vg2-like, especially, Dg-Vg2-like was firstly identified in the mites. The expression levels of all these Vg genes were significantly higher in adult females than other stages. Following blood feeding, the expression levels of these genes increased significantly, followed by a subsequent decrease, aligning with egg production. Silencing Dg-Vgs by RNA interference (RNAi) led to decreased fecundity and egg hatching rates, as well as abnormal embryonic development, suggesting a vital role for Dg-Vgs in both egg formation and embryonic development. Furthermore, the knockdown of Dg-TOR significantly reduced the expression of Dg-Vgs and negatively impacted the reproductive capabilities of PRMs, indicating that TOR influences PRM reproduction by regulating the expression of Dg-Vgs. In summary, these findings demonstrated the crucial roles of Dg-Vgs and Dg-TOR in PRM reproduction, highlighting their potential as targets for pest control.
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  • 文章类型: Journal Article
    水稻产量约占农业利用的淡水资源的一半,导致淹没稻田的甲烷(CH4)等温室气体排放。为了应对这一挑战,环保和经济有效的节水技术已在水稻种植中广泛采用。然而,在水稻中实施节水处理(WST)与高达50%的大量产量损失以及氮利用效率(NUE)的降低有关。在这项研究中,我们发现在WST条件下,水稻中雷帕霉素(TOR)信号通路的靶标受到了损害。通过多聚体谱分析偶联转录组测序(polysome-seq)分析,我们观察到与TOR活性下调相关的WST的全球翻译显著减少.分子,生物化学,遗传分析揭示了对阳性TOR-S6K-RPS6和阴性TOR-MAF1模块对WST下翻译抑制的影响的新见解。有趣的是,铵通过增强TOR信号传导表现出更大的缓解WST下生长限制的能力,同时促进了铵和氮分配的吸收和利用。我们进一步证明,TOR通过5'非翻译区(5'UTR)在翻译水平上调节铵转运蛋白AMT1;1以及氨基酸通透酶APP1和二肽转运蛋白NPF7.3。总的来说,这些发现表明,增强TOR信号可以通过调节蛋白质合成和NUE的过程来减轻WST导致的水稻产量损失。本研究将有助于选育提高水肥利用率的水稻新品种。
    Rice production accounts for approximately half of the freshwater resources utilized in agriculture, resulting in greenhouse gas emissions such as methane (CH4) from flooded paddy fields. To address this challenge, environmentally friendly and cost-effective water-saving techniques have become widely adopted in rice cultivation. However, the implementation of water-saving treatments (WSTs) in paddy-field rice has been associated with a substantial yield loss of up to 50% as well as a reduction in nitrogen use efficiency (NUE). In this study, we discovered that the target of rapamycin (TOR) signaling pathway is compromised in rice under WST. Polysome profiling-coupled transcriptome sequencing (polysome-seq) analysis unveiled a substantial reduction in global translation in response to WST associated with the downregulation of TOR activity. Molecular, biochemical, and genetic analyses revealed new insights into the impact of the positive TOR-S6K-RPS6 and negative TOR-MAF1 modules on translation repression under WST. Intriguingly, ammonium exhibited a greater ability to alleviate growth constraints under WST by enhancing TOR signaling, which simultaneously promoted uptake and utilization of ammonium and nitrogen allocation. We further demonstrated that TOR modulates the ammonium transporter AMT1;1 as well as the amino acid permease APP1 and dipeptide transporter NPF7.3 at the translational level through the 5\' untranslated region. Collectively, these findings reveal that enhancing TOR signaling could mitigate rice yield penalty due to WST by regulating the processes involved in protein synthesis and NUE. Our study will contribute to the breeding of new rice varieties with increased water and fertilizer utilization efficiency.
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  • 文章类型: Journal Article
    雷帕霉素(TOR)途径的高度保守靶标在跨物种的衰老中起着重要作用。先前的研究已经确定,抑制TOR复合物1(TORC1)可显着延长秀丽隐杆线虫的寿命。然而,目前尚不清楚TORC1扰动是否以时空方式影响衰老。在这里,我们应用了生长素诱导降解(AID)工具来敲除内源性DAF-15,即调节相关蛋白TOR(Raptor)的秀丽隐杆线虫直系同源物,表征其在衰老中的作用。在发育过程中对DAF-15的全局或组织特异性抑制会导致各种生长缺陷,而成年期DAF-15的神经元特异性敲除可显着延长寿命和健康时间。神经元DAF-15缺乏诱导的长寿需要DAF-16/FOXO和PHA-4/FOXA转录因子的肠道活动,以及AAK-2/AMP激活的蛋白激酶(AMPK)α催化亚基。转录组分析显示神经元DAF-15敲低促进参与保护的基因的表达。这些发现定义了TORC1在健康衰老中的组织特异性作用,并强调了神经元调节衰老的重要性。
    The highly conserved target of rapamycin (TOR) pathway plays an important role in aging across species. Previous studies have established that inhibition of the TOR complex 1 (TORC1) significantly extends lifespan in Caenorhabditiselegans. However, it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner. Here, we apply the auxin-inducible degradation tool to knock down endogenous DAF-15, the C. elegans ortholog of regulatory associated protein of TOR (Raptor), to characterize its roles in aging. Global or tissue-specific inhibition of DAF-15 during development results in various growth defects, whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan. The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors, as well as the AAK-2/AMP-activated protein kinase α catalytic subunit. Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection. These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.
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  • 文章类型: Journal Article
    为了确保生存和促进增长,无柄植物已经开发出复杂的内部信号网络,在不同的细胞和器官中量身定制,具有共享和专门的功能,可以响应各种内部和外部线索。一个令人着迷的问题出现了:植物细胞或器官如何诊断它正在经历的空间和时间信息,以知道“我在哪里”,然后能够做出准确的具体响应,以决定“去哪里”和“如何去”,尽管哺乳动物中没有神经系统。从最近对植物中多种营养信号通路的全面研究中汲取灵感,这篇综述的重点是由各种营养传感器和传感器介导的交互式营养信号网络。我们评估并说明了细胞和器官如何对这些交互式植物营养网络中变化的空间和时间信息表现出特定响应的示例。此外,我们阐明了植物利用PTM(翻译后修饰)编码整合不同上游营养信号的潜在机制,从而赋予信号中枢蛋白响应特异性。此外,我们讨论了最近的突破性研究,这些研究证明了调节营养传感和信号作为提高作物产量的有希望的策略的潜力,即使减少了肥料的施用。
    To ensure survival and promote growth, sessile plants have developed intricate internal signaling networks tailored in diverse cells and organs with both shared and specialized functions that respond to various internal and external cues. A fascinating question arises: how can a plant cell or organ diagnose the spatial and temporal information it is experiencing to know \"where I am,\" and then is able to make the accurate specific responses to decide \"where to go\" and \"how to go,\" despite the absence of neuronal systems found in mammals. Drawing inspiration from recent comprehensive investigations into diverse nutrient signaling pathways in plants, this review focuses on the interactive nutrient signaling networks mediated by various nutrient sensors and transducers. We assess and illustrate examples of how cells and organs exhibit specific responses to changing spatial and temporal information within these interactive plant nutrient networks. In addition, we elucidate the underlying mechanisms by which plants employ posttranslational modification codes to integrate different upstream nutrient signals, thereby conferring response specificities to the signaling hub proteins. Furthermore, we discuss recent breakthrough studies that demonstrate the potential of modulating nutrient sensing and signaling as promising strategies to enhance crop yield, even with reduced fertilizer application.
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  • 文章类型: Journal Article
    慢性肝病是肝癌发展的已知危险因素,而microRNA(miRNA)肝脏疗法的发展受到难以将miRNA递送至受损组织的阻碍。近年来,大量研究表明,肝星状细胞(HSC)自噬和外泌体在维持肝脏稳态和改善肝纤维化中起重要作用。此外,HSC自噬与外泌体之间的相互作用也影响肝纤维化的进展。在本文中,我们综述了负载特异性miRNA和自噬的间充质干细胞来源的外泌体(MSC-EVs)的研究进展,以及它们在肝纤维化中的相关信号通路,这将为使用MSC-EV治疗性递送靶向慢性肝病的miRNA提供更可靠的基础。
    Chronic liver disease is a known risk factor for the development of liver cancer, and the development of microRNA (miRNA) liver therapies has been hampered by the difficulty of delivering miRNA to damaged tissues. In recent years, numerous studies have shown that hepatic stellate cell (HSC) autophagy and exosomes play an important role in maintaining liver homeostasis and ameliorating liver fibrosis. In addition, the interaction between HSC autophagy and exosomes also affects the progression of liver fibrosis. In this paper, we review the research progress of mesenchymal stem cell-derived exosomes (MSC-EVs) loaded with specific miRNA and autophagy, and their related signaling pathways in liver fibrosis, which will provide a more reliable basis for the use of MSC-EVs for therapeutic delivery of miRNAs targeting the chronic liver disease.
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  • 文章类型: Journal Article
    TOR(雷帕霉素靶)信号通路,以TOR激酶为核心,调节吸收,分布,通过整合代谢网络和其他信号通路来回收营养,从而参与植物生长-防御权衡。虽然萜类化合物在植物生长中起着重要作用,发展,应激反应,和信号转导。TOR信号通路对植物萜类生物合成的影响还有待详细研究。在这项研究中,用TOR抑制剂AZD8055处理丹参组培苗。结果表明,对照组的根在第8天已经开始生长,而用AZD8055处理的幼苗没有生根迹象。结合前8天TOR信号通路相关基因的表达变化,3号的样本,6th,选择第8天进行RNA-Seq分析。通过RNA-Seq分析,从这三个时期的样本中总共获得了50,689个基因,其中4088个基因表现出差异表达。差异表达基因(DEGs)的功能富集和时间序列分析表明,TOR被抑制后,随着处理时间的延长,TOR信号通路对植物生长相关过程的主要影响逐渐传递。DEGs通路富集分析表明,该基因在萜类化合物的生物合成中,如二萜和类胡萝卜素生物合成途径,可以被监管。与其他阶段相比,与萜类生物合成相关的DEGs主要在S2阶段受到调控。此外,参与萜类骨架生物合成的基因在S2阶段也相当丰富,根据基因集富集分析(GSEA)的结果对unigenes进行分析。抑制TOR信号通路可能影响萜类信号分子的生物合成,抑制赤霉素的生物合成,并促进脱落酸的生物合成。本研究从组学的角度探讨了干扰TOR途径对丹参萜类生物合成的影响,为萜类生物合成途径与药用植物生长-防御权衡之间的相互作用提供了新的见解。
    The TOR (Target of Rapamycin) signaling pathway, which takes TOR kinase as the core, regulates the absorption, distribution, and recycling of nutrients by integrating metabolic network and other signaling pathways, thus participating in the plant growth-defense trade-off. While terpenoids play an important role in plant growth, development, stress response, and signal transduction. The effect of the TOR signaling pathway on terpenoid biosynthesis in plants has yet to be studied in detail. In this study, the tissue culture seedlings of Salvia miltiorrhiza were treated with the TOR inhibitor AZD8055. The results show that the roots of the control group had begun to grow on the 8th day, while the seedlings treated with AZD8055 had no rooting signs. Combined with the expression changes of genes related to the TOR signaling pathway in the first 8 days, samples on the 3rd, 6th, and 8th days were selected for RNA-Seq analysis. Through RNA-Seq analysis, a total of 50,689 unigenes were obtained from the samples of these three periods, of which 4088 unigenes showed differential expression. The function enrichment and time-series analysis of differentially expressed genes (DEGs) showed that the main influence of the TOR signal pathway on plant growth-related processes was gradually transmitted with treatment time after TOR was inhibited. Pathway enrichment analysis of DEGs showed that the genes in the biosynthesis of terpenoids, such as diterpenoid and carotenoid biosynthetic pathways, could be regulated. Compared with other stages, DEGs related to terpenoid biosynthesis were mainly regulated in the S2 stage. In addition, the genes involved in terpenoid skeleton biosynthesis was also considerably enriched in the S2 stage, according to the results of gene set enrichment analysis (GSEA) of unigenes. Inhibition of the TOR signaling pathway may affect the biosynthesis of terpenoid signaling molecules, inhibit gibberellin\'s biosynthesis, and promote abscisic acid\'s biosynthesis. This study has discussed the effect of interfering with the TOR pathway on terpenoid biosynthesis in S. miltiorrhiza from the perspective of omics and provides new insight into the interaction between the terpenoid biosynthesis pathway and the growth-defense trade-off of medicinal plants.
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  • 文章类型: Journal Article
    番茄果实成熟是一个独特的营养和能量代谢过程。雷帕霉素靶蛋白(TOR),真核生物中保守的丝氨酸/苏氨酸蛋白激酶,通过整合营养来控制细胞生长和新陈代谢,能源,和激素信号。然而,目前尚不清楚TOR是否参与果实成熟的调节。这里,我们表明,通过化学或遗传方法对SlTOR的操纵极大地改变了番茄果实成熟的过程。表达模式分析显示,随着果实成熟,SlTOR的转录本下降。此外,通过TOR抑制剂AZD8055抑制SlTOR或通过诱导型RNA干扰抑制其转录物加速果实成熟并导致对果实成熟度的总体影响,包括颜色和新陈代谢的变化,水果软化,和成熟相关基因的表达。全基因组转录表明沉默SlTOR重编程与成熟相关的转录谱,如细胞壁和植物激素途径,特别是,提高了乙烯生物合成基因(SlACS2,SlACS4和SlACO1)的表达,并进一步促进了乙烯的生产。相比之下,乙烯作用抑制剂1-MCP即使在SlTOR抑制下也能有效阻断果实成熟。这些结果表明,由SlTOR抑制引起的加速果实成熟取决于乙烯,并且SlTOR可能在乙烯代谢中起调节剂的作用。
    Tomato fruit ripening is a unique process of nutritional and energy metabolism. Target of rapamycin (TOR), a conserved serine/threonine protein kinase in eukaryotes, controls cell growth and metabolism by integrating nutrient, energy, and hormone signals. However, it remains unclear whether TOR participates in the modulation of tomato fruit ripening. Here, we showed that the manipulation of SlTOR by chemical or genetic methods greatly alters the process of tomato fruit maturation. Expression pattern analysis revealed that the transcripts of SlTOR declined as fruit ripening progressed. Moreover, suppression of SlTOR by TOR inhibitor AZD8055 or knock down of its transcripts by inducible RNA interference, accelerated fruit ripening, and led to overall effects on fruit maturity, including changes in colour and metabolism, fruit softening, and expression of ripening-related genes. Genome-wide transcription analysis indicated that silencing SlTOR reprogrammed the transcript profile associated with ripening, including cell wall and phytohormone pathways, elevated the expression of ethylene biosynthetic genes, and further promoted ethylene production. In contrast, the ethylene action inhibitor 1-MCP efficiently blocked fruit maturation, even following SlTOR inhibition. These results suggest that accelerated fruit ripening caused by SlTOR inhibition depends on ethylene, and that SlTOR may function as a regulator in ethylene metabolism.
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  • 文章类型: Journal Article
    雷帕霉素靶蛋白(TOR)是一种丝氨酸/苏氨酸蛋白激酶,在细胞增殖中起着中枢调控作用,增长,和新陈代谢,但是对小球藻中的TOR信号通路知之甚少。在这项研究中,分离并鉴定了一种小球藻DP-1菌株,并对其营养成分进行了分析。基于同源序列分析,保守的CsTOR蛋白存在于小球藻基因组中。此外,存在TOR复合物1(TORC1)的关键成分,但是在小球藻中没有TORC2的成分(RICTOR和SIN1)。药理实验表明,小球藻DP-1对雷帕霉素不敏感,Torin1和KU0063794,而AZD8055可以显著抑制小球藻的生长。RNA-seq分析表明,CsTOR调节AZD8055处理的小球藻DP-1中的各种代谢过程和信号转导途径。在CsTOR抑制下,小球藻DP-1中参与光合作用和碳固定的大多数基因显着下调,表明CsTOR正向调节小球藻的光合作用。此外,CsTOR通过正向调节核糖体合成和负向调节自噬来控制蛋白质的合成和降解。这些观察表明CsTOR在光合作用和细胞代谢中起重要作用。并为小球藻中CsTOR的功能提供了新的见解。
    Target of rapamycin (TOR) is a serine/threonine protein kinase that plays a central regulating role in cell proliferation, growth, and metabolism, but little is known about the TOR signaling pathway in Chlorella sorokiniana. In this study, a Chlorella sorokiniana DP-1 strain was isolated and identified, and its nutritional compositions were analyzed. Based on homologous sequence analysis, the conserved CsTOR protein was found in the genome of Chlorella sorokiniana. In addition, the key components of TOR complex 1 (TORC1) were present, but the components of TORC2 (RICTOR and SIN1) were absent in Chlorella sorokiniana. Pharmacological assays showed that Chlorella sorokiniana DP-1 was insensitive to rapamycin, Torin1 and KU0063794, whereas AZD8055 could significantly inhibit the growth of Chlorella sorokiniana. RNA-seq analysis showed that CsTOR regulated various metabolic processes and signal transduction pathways in AZD8055-treated Chlorella sorokiniana DP-1. Most genes involved in photosynthesis and carbon fixation in Chlorella sorokiniana DP-1 were significantly downregulated under CsTOR inhibition, indicating that CsTOR positively regulated the photosynthesis in Chlorella sorokiniana. Furthermore, CsTOR controlled protein synthesis and degradation by positively regulating ribosome synthesis and negatively regulating autophagy. These observations suggested that CsTOR plays an important role in photosynthesis and cellular metabolism, and provide new insights into the function of CsTOR in Chlorella sorokiniana.
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  • 文章类型: Review
    为了生存和维持增长,无柄植物已经开发了复杂的内部信号网络,可以响应各种外部和内部线索。尽管营养和激素信号在植物生长发育中起着核心作用,激素驱动的过程如何与代谢状态协调仍然是一个谜。雷帕霉素靶蛋白(TOR)激酶是一种进化保守的整合能量的主调节因子,营养素,生长因子,激素和应激信号促进所有真核生物的生长。受最近综合系统的启发,化学,植物TOR的遗传和基因组研究,这篇综述通过在复杂的营养和激素信号网络中整合动态信息,讨论了TOR作为全球定位系统在时间和空间上指导植物生长和发育程序的潜在作用。我们进一步评估和描绘了可能的功能和机制模型,用于单个蛋白激酶TOR如何识别,整合甚至区分过多的正和负输入信号,以通过多个伙伴和效应器执行适当和不同的下游生物过程。
    To survive and sustain growth, sessile plants have developed sophisticated internal signalling networks that respond to various external and internal cues. Despite the central roles of nutrient and hormone signaling in plant growth and development, how hormone-driven processes coordinate with metabolic status remains largely enigmatic. Target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrients, growth factors, hormones, and stress signals to promote growth in all eukaryotes. Inspired by recent comprehensive systems, chemical, genetic, and genomic studies on TOR in plants, this review discusses a potential role of TOR as a \'global positioning system\' that directs plant growth and developmental programs both temporally and spatially by integrating dynamic information in the complex nutrient and hormonal signaling networks. We further evaluate and depict the possible functional and mechanistic models for how a single protein kinase, TOR, is able to recognize, integrate, and even distinguish a plethora of positive and negative input signals to execute appropriate and distinct downstream biological processes via multiple partners and effectors.
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