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Molecular mechanisms of auxin response

生长素反应的分子机制

基本信息

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
项目类别：
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

项目摘要

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.

项目总结