MECHANISMS OF ACTION OF THE MAMMARY ONCOGENE WNT 1

描述：Wnt-1是一种乳腺癌基因，可引起乳腺增生， 在小鼠乳腺中激活时的肿瘤发生， 在培养中某些乳腺上皮细胞的转化。 基因 在胎儿脑形态发生中正常发挥作用。 Wnt-1编码一个 在细胞间信号传递中起作用的分泌蛋白质。 这个目标 研究计划是研究Wnt-1在 乳腺细胞转化，使用两个最近确定的来源， 可溶性Wnt-1蛋白。 Wnt-1蛋白的活性形式和任何 相关因素将被表征，并用于早期调查 乳腺细胞中对Wnt-1的分子反应，并鉴定和 表征Wnt受体。 Wnt信号对斑珠蛋白的影响 和β-连环蛋白，以及其他哺乳动物同源物 果蝇中Wnt-1信号通路的组成部分。 响应Wnt-1快速酪氨酸磷酸化的蛋白质 将被定性。 放射性标记的Wnt-1将用于证明 与细胞特异性结合并通过交联鉴定受体， 亲和标记

DESCRIPTION: Wnt-1 is a mammary oncogene which causes hyperplasia and tumorigenesis when activated in mouse mammary gland and causes transformation of certain mammary epithelial cells in culture. The gene normally functions in fetal brain morphogenesis. Wnt-1 encodes a secreted protein that acts in cell-cell signalling. The goal of this research proposal is to investigate the mechanism of action of Wnt-1 in mammary cell transformation, using two recently identified sources of soluble Wnt-1 proteins. The active form of Wnt-1 protein and any associated factors will be characterized, and used to investigate early molecular responses to Wnt-1 in mammary cells, and to identify and characterize Wnt receptors. The effects of Wnt signals on plakoglobin and beta-catenin will be evaluated, as well as other mammalian homologs of components of the putative Wnt-1 signaling pathway in Drosophila. Proteins that are rapidly tyrosine phosphorylated in response to Wnt-1 will be characterized. Radiolabeled Wnt-1 will be used to demonstrate specific binding to cells and to identify receptors by cross-linking and affinity labeling.