Control of cell morphogenesis and cell growth by conserved NDR kinase Orb6

保守的 NDR 激酶 Orb6 控制细胞形态发生和细胞生长

• 批准号: 8188085
• 负责人: FULVIA VERDE
• 金额: $ 27.98万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8188085
• 关键词: Address; Alzheimer' s Disease; Architecture; Binding; Biochemical; Caenorhabditis elegans; Cell Polarity; Cell Proliferation; Cell Shape; Cell Surface Extensions; Cell membrane; Cell physiology; Cells; Cellular Morphology; Cytoskeleton; Defect; Dendrites; Dendritic Spines; Drosophila genus; Epithelial; Epithelial Cells; Eukaryotic Cell; Fission Yeast; Genetic; Genetic Screening; Genetic Translation; Genomics; Goals; Growth; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate Phosphohydrolases; Homologous Gene; Human; Hybrids; In Vitro; Laboratories; Link; Malignant Neoplasms; Mammals; Mass Spectrum Analysis; Mediating; Membrane Protein Traffic; Messenger RNA; Microscopic; Molecular; Morphogenesis; Morphology; Mus; Mutation; Names; Nature; Neurites; Neuronal Differentiation; Neurons; Normal tissue morphology; Nutritional; Organism; Pathway interactions; Phenotype; Phosphoric Monoester Hydrolases; Phosphorylation; Phosphotransferases; Play; Process; Prostatic Neoplasms; Protein Biosynthesis; Proteomics; Public Health; RNA-Binding Proteins; Regulation; Research; Research Project Grants; Role; Scientist; Signal Pathway; Signal Transduction; Stomach Neoplasms; Synaptic plasticity; T-Cell Lymphoma; Testing; Therapeutic Intervention; Tissues; Translational Repression; Transport Vesicles; Tumor Suppressor Proteins; Yeasts; axon regeneration; carcinogenesis; cell growth; cell motility; cellular targeting; deprivation; improved; insight; kidney cell; novel; polarized cell; polymerization; prevent; programs; rad24 protein; response; tumorigenesis

DESCRIPTION (provided by applicant): Cell polarity is essential for cell morphogenesis, cell migration, and for normal tissue architecture. It involves the dynamic coordination of many cellular processes such as cytoskeletal polymerization, protein synthesis and membrane trafficking. Although substantial progress has been made in our understanding of cell morphogenesis, many of the molecular mechanisms involved in this process are still unknown. The long-term goal of our laboratory is to understand the cellular functions that govern cell shape, and in particular the signaling networks that coordinate cell polarity with cell growth. The conserved NDR kinase plays a key role in the control of cell morphology and cell proliferation in several organisms ranging from yeast to mammals. Currently, there is a very limited understanding of the cellular functions of this conserved kinase and of its targets in the control of cell morphogenesis. We have recently discovered a role for the fission yeast NDR kinase Orb6 in the spatial control of Cdc42 GTPase, a key morphology control factor. Using both hypothesis-driven studies as well as genomic-scale and proteomic approaches; we will dissect the function of Orb6 kinase and identify its targets in the control of cell morphogenesis. The objective of this project is to define the mechanisms whereby NDR kinase spatially regulates cell shape. PUBLIC HEALTH RELEVANCE: Loss of cell polarity and disruption of tissue architecture is a common histological feature in cancer, and emerging evidence is revealing a key role of cell polarity control pathways in the alteration of tissue organization during tumorigenesis. The results of this research project will provide insight into a novel signaling pathway with a conserved function in the control of cell morphogenesis. PUBLIC HEALTH RELEVANCE: The conserved NDR kinase is an enzyme that controls cell shape in many organisms ranging from yeast to mammals. Recently NDR kinase has been recognized as a novel tumor suppressor. Loss of human NDR kinase expression has been detected in T cell lymphoma, gastric tumor and prostate tumor samples. The mechanism by which NDR kinases controls cell shape and cell growth is not known. This project proposes to study the cell shape and cell growth functions of NDR kinase with the long-term goal to identify novel diagnostic markers or novel therapeutic targets in the treatment of cancer.

描述（由申请方提供）：细胞极性对于细胞形态发生、细胞迁移和正常组织结构至关重要。它涉及许多细胞过程的动态协调，如细胞骨架聚合，蛋白质合成和膜运输。虽然我们对细胞形态发生的理解已经取得了实质性的进展，但参与这一过程的许多分子机制仍然是未知的。我们实验室的长期目标是了解控制细胞形状的细胞功能，特别是协调细胞极性与细胞生长的信号网络。 保守的NDR激酶在从酵母到哺乳动物的多种生物体中的细胞形态和细胞增殖的控制中起关键作用。目前，对这种保守激酶的细胞功能及其在细胞形态发生控制中的靶点的了解非常有限。我们最近发现了裂变酵母NDR激酶Orb6在空间控制Cdc42 GTb3中的作用，Cdc42 GTb3是一个关键的形态控制因子。使用假设驱动的研究以及基因组规模和蛋白质组学方法，我们将剖析Orb6激酶的功能，并确定其在细胞形态发生控制中的靶点。本项目的目的是确定NDR激酶空间调节细胞形状的机制。 公共卫生相关性：细胞极性的丧失和组织结构的破坏是癌症中常见的组织学特征，并且新出现的证据揭示了细胞极性控制途径在肿瘤发生期间组织结构改变中的关键作用。该研究项目的结果将提供一个新的信号通路与保守的功能，在控制细胞形态发生的洞察力。 公共卫生相关性：保守的NDR激酶是一种在从酵母到哺乳动物的许多生物体中控制细胞形状的酶。近年来，NDR激酶被认为是一种新的肿瘤抑制因子。已经在T细胞淋巴瘤、胃肿瘤和前列腺肿瘤样品中检测到人NDR激酶表达的缺失。NDR激酶控制细胞形状和细胞生长的机制尚不清楚。本项目旨在研究NDR激酶的细胞形态和细胞生长功能，以确定癌症治疗中新的诊断标志物或新的治疗靶点为长期目标。