Investigating tyrosine phosphorylation of Notch proteins

研究 Notch 蛋白的酪氨酸磷酸化

基本信息

批准号：
10578301
负责人：
Allan R Albig
金额：
$ 40.83万
依托单位：
BOISE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10578301
关键词：
Address Affect Animals Binding Biological Process Biology Blood Vessels Cell Communication Cell Culture Techniques Cell physiology Cells Collaborations Complex Data Disease EGF gene Educational process of instructing Endothelial Cells Endothelium Extracellular Matrix FGF2 gene Fibrosis Genes Genetic Transcription Goals Growth Factor Health Human Hyperglycemia Hypoxia Individual Integrins Ligands Link Modeling Molecular Molecular Biology Mutation NOTCH3 gene Normal Range Nuclear Nuclear Translocation Output Pathologic Phosphorylation Physiological Proteins Publishing Regulation Research Resveratrol Role Science Signal Transduction Site Stimulus Students Sum System Testosterone Tissues Transcriptional Activation Transforming Growth Factor beta Tyrosine Tyrosine Phosphorylation Update Vascular Endothelial Growth Factors Vascular System Work angiogenesis career cell behavior gamma secretase graduate student high school notch protein novel programs response sensor shear stress skills src-Family Kinases undergraduate student

项目摘要

Project Summary Extracellular matrix, integrins, and Notch collectively regulate a host of normal and pathological cellular activities. Evidence emerging from our preliminary studies shows that these cellular entities are coordinated into a signaling mechanism that has not been previously observed. The implications of our observation are broad and likely to have deep impacts on our understanding of cell interactions within cellular microenvironments as well as cellular behaviors in a range of normal and pathological scenarios. In this renewal application, we investigate the hypothesis that Notch tyrosine phosphorylation regulates angiogenesis. To address this hypothesis, we have proposed two aims that dig deeper into the molecular regulation of Notch activity through tyrosine phosphorylation by Src kinase, and to understand how Notch tyrosine phosphorylation impacts angiogenesis and vascular function. Throughout these studies and in the spirit of the AREA program, we will engage high school, undergraduate, and graduate students to build scientific confidence and teach skills these students will require in order to pursue careers in science. At the conclusion of our studies, we will have accomplished two important milestones towards understanding this novel regulatory mechanism. Specifically, we will have unraveled many molecular details describing how Src controls Notch, and we will have defined the importance of this signaling cascade to vascular biology. Since both Notch and vascular biology operate in a wide variety of normal and disease states, our work is highly relevant to the promotion of human health.

项目概要细胞外基质、整合素和 Notch 共同调节许多正常和病理的细胞细胞活动。我们的初步研究中出现的证据表明，这些细胞实体被协调成以前未观察到的信号机制。这我们的观察的影响是广泛的，并且可能对我们的理解产生深远的影响细胞微环境中的细胞相互作用以及一系列细胞行为正常和病理情况。在此更新应用程序中，我们研究了假设 Notch酪氨酸磷酸化调节血管生成。为了解决这个假设，我们提出了两个目标，通过以下方式更深入地研究Notch活性的分子调控： Src 激酶对酪氨酸进行磷酸化，并了解 Notch 酪氨酸磷酸化的过程影响血管生成和血管功能。通过这些研究并本着 AREA 计划，我们将聘请高中生、本科生和研究生来构建这些学生为了追求职业生涯所需的科学信心和教学技能科学。在我们的研究结束时，我们将实现两个重要的里程碑理解这种新颖的调节机制。具体来说，我们将解开许多分子细节描述了 Src 如何控制 Notch，我们将定义这种信号级联对血管生物学的重要性。由于Notch和血管生物学在各种正常和疾病状态下运行，我们的工作与促进人类健康。