Receptor Tyrosine Kinase Activity in Drosophila Eye Development

果蝇眼睛发育中的受体酪氨酸激酶活性

• 批准号: 9336911
• 负责人: ANDREW TOMLINSON
• 金额: $ 32万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9336911
• 关键词: Alpha Cell; Arteriosclerosis; Behavior; Biochemical; Biological; Biological Assay; Biological Models; Biology; Cell membrane; Cell physiology; Cells; Complex; Computers; Development; Diabetes Mellitus; Diffuse; Disease; Drosophila eye; Drosophila genus; Endocytosis; Endocytosis Pathway; Ensure; Epidermal Growth Factor Receptor; Eye Development; Gene Targeting; Hydrophobicity; Individual; Integral Membrane Protein; Ligands; Link; Malignant Neoplasms; Maps; Membrane Proteins; Molecular; Molecular Profiling; N-terminal; Nature; Pathway interactions; Peptide Signal Sequences; Peptides; Photoreceptors; Play; Receptor Activation; Receptor Protein-Tyrosine Kinases; Regulation; Reproducibility; Research; Role; Signal Pathway; Signal Transduction; Solid; Specific qualifier value; Structure; To specify; Transmembrane Domain; Tyrosine Phosphorylation; base; cell type; design; experimental study; genetic approach; programs; receptor; tissue culture; tool; transcription factor

Project Summary Receptor Tyrosine Kinases (RTKs) play profound and pervasive roles in biology and are associated with many different cancers, and are currently the focus of intense research. For practical reasons, most RTK studies are carried out in tissue culture which has both advantages and limitations. One limitation is that these studies do not examine RTKs in their native biological setting, and a deep understanding of how they perform their normal functions is often lacking. This application uses the developing Drosophila eye as a setting in which to study two distinctly different RTKs in their normal biological roles. One is the Drosophila EGF receptor (DER), which by structure and behavior is a standard RTK: it is a simple plasma membrane protein expressed ubiquitously at low levels, its ligand is a diffusible peptide, and its activation occurs on the plasma membrane. The other is Sevenless (Sev), an RTK with a number of unusual features. It has a multimeric structure, it is expressed at high levels and transduces a potent RTK signal, its ligand is an integral membrane protein, and its activation is linked to endocytosis which occurs in a cell-type specific manner. These features of Sev reflect its use by the developmental program to generate a high RTK signal in one specific photoreceptor precursor. Here we compare and contrast the structure and regulation of the two RTKs to understand how the unusual features of Sev allow it to perform its specific functions.

项目摘要 受体酪氨酸激酶(RTK)在生物学中发挥着深远而普遍的作用，并且 与许多不同的癌症有关，目前是密集研究的焦点。为 由于实际原因，大多数RTK研究是在组织培养中进行的，组织培养既有组织培养又有组织培养 优势和局限性。一个限制是，这些研究没有检查RTK在 他们的原生生物背景，以及对他们如何表现正常的深刻理解 功能常常缺失。这个应用程序使用正在发育的果蝇眼睛作为设置 研究两种截然不同的RTK在其正常生物学作用中的作用。一个是 果蝇EGF受体(DER)，在结构和行为上是一个标准的RTK：它是一种 简单的质膜蛋白在低水平表达，其配体是一种 可扩散的多肽，其激活发生在质膜上。另一个是 Seven less(Sev)，一款具有许多不同寻常功能的RTK。它有一个多聚体结构，它 在高水平表达，并传递一个强大的RTK信号，其配体是一个积分 膜蛋白，它的激活与细胞类型中发生的内吞作用有关 具体的方式。SEV的这些特征反映了开发计划使用它来 在一个特定的光感受器前体中产生高RTK信号。在这里，我们比较和 对比两个RTK的结构和监管，以了解不寻常的 SEV的功能使其能够执行其特定功能。