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.

项目摘要细胞外基质，整联蛋白和缺口集体调节正常和病理的宿主细胞活动。我们的初步研究提出的证据表明，这些细胞实体被协调为先前尚未观察到的信号传导机制。这我们观察的含义广泛，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范围内的细胞行为正常和病理方案。在此续签应用中，我们研究了假设那种缺口酪氨酸磷酸化调节血管生成。为了解决这一假设，我们提出了两个通过 SRC激酶的酪氨酸磷酸化，并了解Notch酪氨酸磷酸化如何影响血管生成和血管功能。在这些研究中，本着区域计划，我们将与高中，本科生和研究生一起建造这些学生将需要的科学信心和教学技能才能从事职业科学。在我们的研究结束时，我们将完成两个重要的里程碑要理解这种新颖的监管机制。具体来说，我们将解开许多分子细节描述了SRC如何控制缺口，我们将定义该信号级联对血管生物学的重要性。由于缺口和血管生物学我们的工作在多种正常状态和疾病状态下，与促进人类健康。