CEK8--A NOVEL NEURAL RECEPTOR TYROSINE KINASE

CEK8--一种新型神经受体酪氨酸激酶

• 批准号: 6272153
• 负责人: ELENA B PASQUALE
• 金额: $ 20.46万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6272153
• 关键词: antireceptor antibody; binding proteins; biological signal transduction; cadherins; cell cell interaction; chick embryo; developmental neurobiology; embryo /fetus tissue /cell culture; enzyme activity; genetic library; growth cones; laboratory rabbit; laboratory rat; ligands; molecular cloning; neural cell adhesion molecules; neurogenesis; neuronal guidance; neurons; phosphorylation; protein structure function; protein tyrosine kinase; proteoglycan; receptor expression; western blottings

Cek8 (Chicken embryo kinase 8) is a recently identified receptor-type tyrosine kinase of the Eph subclass which is preferentially expressed in neural tissues. The extracellular domain of Cek8 contains motifs characteristic of cell adhesion molecules, while the cytoplasmic domain comprises a typical tyrosine kinase catalytic domain. Preliminary data indicate that Cek8 and its mammalian homologs may function to regulate cellular interactions and axonal growth in the developing nervous system. Furthermore, Cek8 may be implicated in the formation of tumors of the nervous system. The objectives of the proposed research are to provide insight into the neural functions of Cek8 by using a variety of different molecular approaches. The cellular and subcellular localization of Cek8 in the nervous system of the developing embryo and in dissociated neural cultures will be studied in detail, together with the developmental regulation and level of catalytic activation of Cek8 in vivo. For example, the possibility that Cek8 may be concentrated in growth cones and implicated in axonal guidance will be explored. These studies will provide the initial clues about the functions of Cek8. The molecular components of the signaling pathways in which Cek8 is implicated will be dissected by investigating the interactions of Cek8 with molecules that have a similar localization in the nervous system. Neuronal adhesion molecules, proteoglycans and cytoplasmic tyrosine kinases are among the known molecules that may participate in functional interactions with Cek8. Other molecules interacting with Cek8, such s ligands or substrates, will also be searched for based on their ability to bind to Cek8. Finally, the expression and activity of Cek8 will be perturbed with antibodies, a dominant negative form of Cek8, Cek8 antisense sequences and, if identified, the Cek8 activating lignad. These studies will be performed in vivo and in vitro to address directly the functions of Cek8, particularly during axonal growth. The characterization of Cek8 and of the molecules that interact with it, which will be addressed in the proposed studies, will provide the information necessary to manipulate the neural signal transduction pathways in which Cek8 is implicated. Thus, the studies proposed are likely to form the basis for the development of treatments to ameliorte specific developmental neural pathologies and degenerative diseases of the nervous system.

鸡胚激酶8（Chicken embryo kinase 8，Cek8）是最近发现的一种受体型激酶， Eph亚类的酪氨酸激酶，其优先表达于 神经组织 Cek8的胞外结构域含有基序 细胞粘附分子的特征，而细胞质结构域 包括典型的酪氨酸激酶催化结构域。 初步数据 表明Cek8及其哺乳动物同源物可能具有调节 在发育中的神经系统中的细胞相互作用和轴突生长。 此外，Cek8可能与肿瘤的形成有关。 神经系统 拟议研究的目标是提供 通过使用各种不同的方法来深入了解Cek 8的神经功能， 分子方法 Cek 8在大肠杆菌中的细胞和亚细胞定位 发育中胚胎的神经系统和分离的神经系统 文化将被详细研究，连同发展 调节和体内Cek8的催化活化水平。 比如说， Cek 8可能集中在生长锥中， 将探索与轴突导向有关的问题。 这些研究将提供 关于Cek 8功能的最初线索。 的分子组分 涉及Cek8的信号传导途径将通过以下方式进行剖析： 研究Cek8与具有类似分子的相互作用， 定位在神经系统中。 神经元粘附分子， 蛋白聚糖和细胞质酪氨酸激酶是已知的 这些分子可能参与与Cek8的功能性相互作用。 其他 与Cek 8相互作用的分子，如s配体或底物，也将被 根据它们与Cek 8结合的能力进行搜索。 最后 Cek8的表达和活性将被抗体干扰， Cek8、Cek8反义序列的显性阴性形式，并且，如果 Cek8激活lignad。 这些研究将在 体内和体外直接解决Cek8的功能，特别是 在轴突生长的过程中。 Cek 8和分子的表征 与之相互作用，这将在拟议的研究中得到解决， 将提供操纵神经信号所需的信息 其中涉及Cek8的转导途径。 因此，研究 提出的可能形成治疗发展的基础， 改善特定的发育神经病理和退行性 神经系统疾病。