STRUCTURE AND FUNCTION OF FRIZZLED LIKE PROTEINS IN SKELETAL DEVELOPMENT

一系列意想不到的令人兴奋的事件已经发展， frzb基因的功能研究。发现卷曲的 蛋白质是原癌基因Wnt家族的受体家族。 Wnt蛋白是一种信号分子，参与多种 发育和肿瘤过程的影响。 由于高度相似的 Frzb的卷曲样结构域与假定的配体结合结构域 在卷曲受体中，我们假设Frzb也会与 关于WNTS我们成功地证明了这种相互作用， 使用共转染的哺乳动物的一系列免疫沉淀实验 细胞我们确定了Frzb/Wnt相互作用的关键结构域， 表明这种直接相互作用导致Xwnt 8的失活 当共注射到非洲爪蟾体内时。 发现Frzb可以作为 分泌的Wnt活性拮抗剂代表了 研究Wnt信号。 为了进一步分析Frzb的作用， 颅面和骨骼发育，我们正在进行组织特异性 使用同源重组和Cre- loxp系统 Frzb基因在乳腺癌不同阶段的靶向缺失 发展应该提供重要的信息，其生理 作用

An unexpected series of exciting events has evolved with regard to the functional studies of the frzb gene. It was found that the frizzled proteins are a family of receptors for the Wnt family of proto-oncogenes. Wnt proteins are signalling molecules which participate in a wide variety of developmental and neoplastic processes. Given the high similarity of the frizzled-like domain of Frzb with the presumed ligand binding domain of the frizzled receptors, we hypothesized that Frzb would also interact with Wnts. We were successful in demonstrating this interaction by a series of immunoprecipitation experiments using co-transfected mammalian cells. We identified the critical domains for the Frzb/Wnt interaction and showed that this direct interaction results in the inactivation of Xwnt8 in vivo when co-injected in Xenopus. The discovery that Frzb can act as a secreted antagonist of Wnt activity represents a major leap forward in research into Wnt signaling. To further analyze the role of Frzb in craniofacial and skeletal development we are conducting tissue-specific gene targeting studies in mice using homologous recombination and the Cre- loxp system. The targeted deletion of Frzb at different stages of development should provide important information on its physiological role.