BINDING AND FUNCTIONS OF RECEPTOR TYROSINE PHOSPHATASE B

细胞酪氨酸磷酸化在控制血管紧张素转换酶中起关键作用 正常发育和肿瘤形成。RPTPβ是一种受体蛋白 酪氨酸磷酸酶在胶质细胞中的表达模式表明 在神经系统的形态发生和可塑性中的作用。此外， 该蛋白与细胞外基质蛋白Tenascin结合 神经细胞黏附分子N-CAM和Ng。CAM/L1。这样做的目的是 项目是分析RPTP Beta与各种配体和 研究这些相互作用对细胞黏附的影响，以及 可能调节神经胶质细胞分化的跨膜信号转导 与神经元的相互作用。第一个具体目标是描述 RPTPβ在组织和细胞中的表达模式及其 在发育过程中与不同配体的相互作用。然后分析 RPTP中不同胞外区的结合特性 将使用编码RPTP Beta中不同区域的Beta cDNA构建 表达分泌型和膜锚定型RPTPβ 将其导入哺乳动物细胞。分泌物的分子结合分析 细胞上表达的形式及其细胞黏附分析 表面将被用来分析哪些区域对于结合是重要的 RPTPβ结合到不同的配体，如Tenascin和Ng-CAM/L1。为了测试 RPTPβ及其不同结构域在细胞中的潜在功能 分子克隆技术将用于表达或抑制 RFTPβ的表达。在每种情况下，治疗的效果将是 分析以检测RPTP Beta表达的变化 与细胞对配体反应的变化相关(即 Tenascin和Ng-CAM)，包括细胞黏附、细胞形状和细胞 组织。RPTPβ是第一个被鉴定的受体/磷酸酶 异亲性配体，因此研究它是很重要的 与RPTPβ结合的配体是否参与信号转导 通过改变磷酸酶的比活性，通过引起 重新分配磷酸酶以改变其局部活性，或通过 改变RPTPβ的表达模式。这种实验性的方法 将提供有关RPTP结合区结构的新信息 β可能参与正常和正常皮肤的黏附和生长调节 转化的星形胶质细胞。这一结果也可能提供重要的 了解放射状胶质细胞和星形胶质细胞发育的线索， 以及它们与发育中的神经元的相互作用，以及 RPTPβ在脑肿瘤生长中的作用

Cellular tyrosine phosphorylation plays a crucial role in the control of normal development and neoplasia. RPTP beta is a receptor protein tyrosine phosphatase that is expressed in glia in a pattern suggesting a role in morphogenesis and plasticity of the nervous system. Moreover, this protein binds to the extracellular matrix protein tenascin and to the neural cell adhesion molecules N-CAM and Ng. CAM/L1. The goal of this project is to analyze interactions of RPTP beta with various ligands and to study the consequences of these interactions on cell adhesion, and on transmembrane signalling that may modulate glial differentiation and interactions with neurons. The first specific aim is to characterize the expression patterns of RPTP beta in tissues and cells, and its interactions with different ligands during development. Then to analyze the binding properties of the different extracellular domains in RPTP beta cDNA constructs encoding different regions in RPTP beta will be used to express secreted and membrane-anchored forms of RPTP beta by transfection into mammalian cells. Molecular binding assays for secreted forms and cellular adhesion assays for forms expressed on the cell surface will be used to analyze which domains are important for binding of RPTP beta to different ligands such as tenascin and Ng-CAM/L1. To test potential functions of RPTP beta and its different domains in cells, molecular cloning techniques will be used to express or suppress expression of RFTP beta. In each case, effects of the treatment will be analyzed to detect changes in RPTP beta expression which will be correlated with alterations in cellular responses to ligands (i.e. tenascin and Ng-CAM) including cell adhesion, cell shape and cell division. RPTP beta is the first receptor/phosphatase with identified heterophilic ligands, and therefore it is important to investigate whether ligand binding to RPTP beta is involved in signal transduction by altering the specific activity of the phosphatase, by causing a redistribution of the phosphatase to alter its activity locally, or by changing the pattern of RPTP beta expression. This experimental approach will provide new information on the structure of binding regions of RPTP beta that may be involved in adhesion and growth regulation of normal and transformed astroglial cells. The results may also provide important clues for understanding development of radial glial cells and astrocytes, and their interactions with developing neurons, as well as potential roles of RPTP beta in growth of brain tumors.