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

基本信息

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
项目类别：
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&apos 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

项目摘要

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（由申请人提供）：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，例如细胞骨架聚合，蛋白质合成和膜运输。尽管我们对细胞形态发生的理解已经取得了重大进展，但此过程中涉及的许多分子机制仍然未知。我们实验室的长期目标是了解控制细胞形状的细胞功能，尤其是将细胞极性与细胞生长进行协调的信号网络。保守的NDR激酶在从酵母到哺乳动物的几种生物中的细胞形态和细胞增殖中的控制中起关键作用。当前，对这种保守激酶的细胞功能及其在控制细胞形态发生中的靶标的细胞功能非常有限。我们最近发现了裂变酵母NDR激酶ORB6在CDC42 GTPase的空间控制中的作用，Cdc42 GTPase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，并确定其在控制细胞形态发生中的靶标。该项目的目的是定义NDR激酶在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的共同组织特征，而新兴的证据揭示了细胞极性控制途径在肿瘤发生过程中组织组织的改变中的关键作用。该研究项目的结果将洞悉具有控制细胞形态发生的新型信号通路。公共卫生相关性：保守的NDR激酶是一种控制许多生物体中细胞形状的酶，从酵母到哺乳动物。最近，NDR激酶被公认为是一种新型的肿瘤抑制剂。在T细胞淋巴瘤，胃肿瘤和前列腺肿瘤样品中已检测到人NDR激酶表达的丧失。 NDR激酶控制细胞形状和细胞生长的机制尚不清楚。该项目提议研究NDR激酶的细胞形状和细胞生长功能，其长期目标是鉴定新的诊断标记或新型治疗靶标在癌症治疗中。