Receptor Tyrosine Kinase Activity in Drosophila Eye Development

项目摘要 受体酪氨酸激酶（RTK）在生物学中起着深刻和普遍的作用， 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研究都是在组织培养中进行的， 优点和局限性。一个局限性是，这些研究没有检查RTK在 他们的原生生物环境，以及对他们如何进行正常活动的深刻理解， 功能往往缺乏。这个应用程序使用发展中的果蝇眼睛作为一个设置 在其中研究两种明显不同的RTK在其正常的生物学作用。一是 果蝇表皮生长因子受体（DER），其结构和行为是一个标准的RTK：它是一个 一种普遍低水平表达的简单质膜蛋白，其配体是一种 它是一种可扩散的肽，其活化发生在质膜上。另一个是 Sevenless（Sev）是一种具有许多不寻常功能的RTK。它具有多聚体结构， 高水平表达并转导有效的RTK信号，其配体是一个整合的 膜蛋白，其激活与细胞类型中发生的内吞作用有关 具体方式。Sev的这些特征反映了其在开发项目中的用途， 在一种特定的感光细胞前体中产生高RTK信号。在这里，我们比较和 对比两个RTK的结构和监管，以了解如何不寻常的 Sev的特性允许其执行其特定功能。

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.