Molecular mechanisms of auxin response

生长素反应的分子机制

• 批准号: 10619609
• 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/10619609
• 关键词: ATP phosphohydrolase; 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; neural; novel; novel strategies; organ growth; overexpression; phosphoproteomics; plant growth/development; protein phosphatase 2C; 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/苏氨酸磷酸化在众多中起着必不可少的调节功能 细胞过程。 2C型蛋白磷酸酶（PP2C）包括一类主要的Ser/Thr磷酸酶 （PPases）和几个人PP2C中的缺陷已在癌症，糖尿病，心血管中隐含 疾病，神经疾病和压力信号传导。但是，了解PP2C的主要差距 酶活性受到调节，哪些特定蛋白质和过程受PP2C的控制。在植物中， PP2C.D PPase通过反映细胞膨胀来抑制器官的生长。部分是由 质膜（PM）H+-ATP酶的关键调节磷酸化的去磷酸化。增长 激素生长素通过诱导小型生长素UP RNA（Saur）基因的表达来刺激细胞膨胀，该基因 编码与PP2C.D PPases结合的新型蛋白质以抑制酶活性。这个长期目标 项目将彻底了解生长素介导的植物控制的分子机制 增长与发展。更具体地说，本提案中描述的工作将确定监管机构和 saur-pp2c.d信号集线器的下游效应参与生长素介导的细胞膨胀和 体积变化与多种细胞过程的整合，以产生协调的生长反应。 磷酸化蛋白质组学研究已经鉴定出> 140种表现出改变磷酸化的蛋白质，以响应于 生长素。该数据集与受Saur过表达影响的磷蛋白实质上重叠，这意味着 Saur-PP2C.D模块是细胞膨胀过程中生长素磷酸瘤的主要调节剂。使用 模型植物拟南芥的强大遗传系统，拟议的研究将研究功能 选定磷蛋白候选者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。还将对生长素对PM H+-ATPase活性的调节进行详细分析。 生长素都通过pp2c.d活性抑制H+-ATPase去磷酸化并刺激 通过TMK1和其他激酶促进ATPase磷酸化来激活，包括WNK的直系同源物 和SPAK/OSR激酶在哺乳动物细胞大小控制中实施。所有这些激酶与一个激酶相互作用 另一个和PP2C.D PPases，研究将解决激酶和磷酸酶活性如何 协调和相互监管。这项工作将阐明PP2C功能和调节机制， 识别PP2C.D的效果，可调节细胞的扩展，并照亮生长素如何坐在多种细胞 控制细胞尺寸的过程。鉴于跨王国和普遍的PP2C功能的保护 细胞大小控制过程，项目发现将产生广泛的影响，包括对人类的影响 发展与疾病。此外，由于人类依靠植物来源于食物，纤维和 拟议的研究将通过Saur-PP2C.D调节阐明植物的生长控制 模块和促进了操纵植物生长以使人类健康的新型策略。