Molecular mechanisms of auxin response

生长素反应的分子机制

• 批准号: 10404759
• 负责人: WILLIAM M GRAY
• 金额: $ 38.75万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10404759
• 关键词: ATP phosphohydrolase; Address; Affect; Arabidopsis; Auxins; Binding Proteins; Biological Models; Biology; Cardiovascular Diseases; Cell Size; Cell membrane; Cell physiology; Cells; Data Set; Defect; Development; Diabetes Mellitus; Disease; Eukaryota; Exhibits; Fiber; Food; Genes; Genetic; Goals; Growth; Growth and Development function; Health; Hormones; Human; Human Development; Link; Malignant Neoplasms; Mammalian Cell; Mediating; Molecular; Orthologous Gene; Pharmacologic Substance; Phosphoproteins; Phosphoric Monoester Hydrolases; Phosphorylation; Phosphotransferases; Plant Model; Plant Sources; Plants; Play; Process; Protein Dephosphorylation; Proteins; Proton-Translocating ATPases; RNA; Regulation; Repression; Research; Role; Serine/Threonine Phosphorylation; Signal Transduction; Somatotropin; Stress; Work; enzyme activity; human disease; novel; novel strategies; organ growth; overexpression; phosphoproteomics; plant growth/development; protein phosphatase 2C; relating to nervous system; response; tool

PROJECT SUMMARY Reversible serine/threonine phosphorylation of proteins plays an essential regulatory function in numerous cellular processes. Type 2C protein phosphatases (PP2Cs) comprise a major class of Ser/Thr phosphatases (PPases), and defects in several human PP2Cs have been implicated in cancer, diabetes, cardiovascular disease, neural disorders, and stress signaling. However, major gaps exist in understanding how PP2C enzyme activity is regulated and what specific proteins and processes are under PP2C control. In plants, PP2C.D PPases inhibit organ growth by repressing cell expansion. In part, this is accomplished by dephosphorylation of a key regulatory phosphosite of plasma membrane (PM) H+-ATPases. The growth hormone auxin stimulates cell expansion by inducing expression of Small Auxin Up RNA (SAUR) genes, which encode novel proteins that bind to PP2C.D PPases to inhibit enzymatic activity. The long-term goal of this project is to thoroughly understand the molecular mechanisms underlying auxin-mediated control of plant growth and development. More specifically, the work described in this proposal will identify regulators and downstream effectors of SAUR-PP2C.D signaling hubs involved in auxin-mediated cell expansion and the integration of volumetric changes with diverse cellular processes to yield a coordinated growth response. Phosphoproteomic studies have identified >140 proteins exhibiting altered phosphorylation in response to auxin. This dataset overlaps substantially with phosphoproteins affected by SAUR overexpression, implicating SAUR-PP2C.D modules as major regulators of the auxin phosphorylome during cell expansion. Using the powerful genetic system of the model plant Arabidopsis, the proposed studies will investigate the functional roles of select phosphoprotein candidates in auxin-induced growth and their regulatory interactions with SAUR- PP2C.D modules. Detailed analysis of auxin’s regulation of PM H+-ATPase activity will also be conducted. Auxin both inhibits H+-ATPase dephosphorylation via SAUR repression of PP2C.D activity and stimulates activation by promoting ATPase phosphorylation by TMK1 and additional kinases, including orthologs of WNK and SPAK/OSR kinases implicated in mammalian cell size control. All of these kinases interact with one another and PP2C.D PPases, and research will address how kinase and phosphatase activities are coordinated and mutually regulated. This work will elucidate PP2C functions and regulatory mechanisms, identify PP2C.D effectors that modulate cell expansion, and illuminate how auxin coordinates diverse cellular processes to control cell size. Given the conservation of PP2C function across kingdoms and the universal process of cell size control, project findings will have broad impact, including implications into human development and disease. Further, as humans depend on plants for sources of food, fiber, and pharmaceuticals, the proposed studies will elucidate plant growth control by SAUR-PP2C.D regulatory modules and facilitate novel strategies for manipulating plant growth to benefit human health.

项目摘要 蛋白质的可逆丝氨酸/苏氨酸磷酸化在许多细胞中起着重要的调节作用。 细胞过程2C型蛋白磷酸酶（PP 2C）包括主要类别的Ser/Thr磷酸酶 PP 2C的缺陷与癌症、糖尿病、心血管疾病、糖尿病、糖尿病和糖尿病的发生有关。 疾病、神经紊乱和压力信号。然而，在理解PP 2C如何 酶的活性受到调节，哪些特定的蛋白质和过程受PP 2C的控制。在植物中， PP 2C. D PPases通过抑制细胞扩增来抑制器官生长。在某种程度上，这是通过 质膜（PM）H+-ATP酶的关键调节磷酸化位点的去磷酸化。生长 激素生长素通过诱导小生长素上调RNA（SAUR）基因的表达来刺激细胞扩增，SAUR基因 编码结合PP 2C. D PPase以抑制酶活性的新蛋白质。长期目标是 该项目旨在深入了解生长素介导的植物调控的分子机制 促进经济增长和发展。更具体地说，本提案所述的工作将确定监管机构， 参与生长素介导的细胞扩增的SAUR-PP 2C.D信号传导枢纽的下游效应物， 体积变化与不同细胞过程的整合，以产生协调的生长反应。 磷酸化蛋白质组学研究已经鉴定了超过140种蛋白质，其响应于磷酸化的改变而表现出磷酸化。 生长素。该数据集与受SAUR过表达影响的磷蛋白基本上重叠，暗示 SAUR-PP 2C.D模块作为细胞扩增过程中生长素磷酸化组的主要调节剂。使用 强大的遗传系统的模式植物拟南芥，拟议的研究将调查功能 选择磷蛋白候选物在生长素诱导的生长中的作用及其与SAUR的调节相互作用， PP2C.D模块。并详细分析了生长素对质膜H ~+-ATPase活性的调节作用。 生长素通过SAUR抑制PP 2C. D活性来抑制H+-ATP酶去磷酸化，并刺激 通过促进由TMK 1和其他激酶（包括WNK的直系同源物）引起的ATP酶磷酸化而激活 和涉及哺乳动物细胞大小控制的SPAK/OSR激酶。所有这些激酶都与一种 另一个和PP2C.D PPases，研究将解决激酶和磷酸酶活性是如何被激活的。 相互协调，相互制约。这项工作将阐明PP 2C的功能和调控机制， 鉴定调节细胞扩增的PP2C.D效应子，并阐明生长素如何协调不同的细胞增殖， 控制细胞大小的过程。考虑到PP 2C功能在不同王国之间的保守性和普遍性， 细胞大小控制的过程中，项目的研究结果将产生广泛的影响，包括对人类的影响， 发展和疾病。此外，由于人类依赖植物作为食物、纤维和营养的来源， 药物，拟议的研究将阐明植物生长控制SAUR-PP 2C.D调节 模块和促进操纵植物生长的新策略，以造福人类健康。