RECEPTOR--TYROSINE PHOSPHATASE LAR IN LUNG DEVELOPMENT

描述(改编自申请者的抽象和具体目标)： 这个项目的目标是定义特定受体的作用 酪氨酸磷酸酶(PTPase)在调节上皮细胞中的作用 发育和成熟肺的增殖和分化。 酪氨酸PTPase使具有以下特征的蛋白质上的磷酸酪氨酸去磷酸化 被特定的酪氨酸激活或失活(磷酸化) 其中许多是生长因子受体。因此，PTPase具有 调节相关的各种细胞信号事件的可能性 与发育和细胞分化有关。申请的前提是 跨膜酪氨酸磷酸酶LAR可能负向调节 与生长因子受体相互作用的细胞生长 固有的酪氨酸激酶活性，这一功能是 在肺上皮细胞中很重要，特别是在肺发育过程中。 具体目标是：1)开发方法和试剂以改变 LAR的生物学活性及其对上皮细胞的影响 胎肺器官培养体系中的增殖和分化； 2)确定LAR在调节细胞增殖中的潜在作用 以及调节生长因子介导的信号转导；3) 通过识别和识别确定LAR功能的具体机制 研究LAR与之相互作用的蛋白质。

DESCRIPTION (Adapted from the applicant's abstract and specific aims): The goal of this project is to define the role that a specific receptor type tyrosine phosphatase (PTPase) plays in regulating epithelial cell proliferation and differentiation in developing and mature lung. Tyrosine PTPases dephosphorylate phospho-tyrosines on proteins that have been activated or inactivated (phosphorylated) by specific tyrosine kinases of which many are growth factor receptors. Thus, PTPases have the potential to regulate a variety of cell signaling events associated with development and cell differentiation. The application postulates that the transmembrane tyrosine phosphatase LAR may negatively regulate cell growth by interacting with growth factor receptors possessing intrinsic tyrosine kinase activities, and that this function is important in lung epithelial cells, especially during lung development. The specific aims are to: 1) develop methods and reagents to alter biological activities of LAR and define their effects on epithelial cell proliferation and differentiation in a fetal lung organ culture system; 2) determine the potential roles of LAR in regulating cell proliferation and in modulating growth factor-mediated signal transduction; and 3) determine specific mechanism of LAR function by identifying and characterizing proteins with which LAR interacts.