CHARACTERIZATION OF A SRC-RELATED GENE IN MACROPHAGES

这个建议的重点是酪氨酸激酶，hck （造血细胞激酶）主要在造血干细胞的细胞中表达。 髓样谱系。 它与酪氨酸的src家族的关系 激酶是基于DNA水平上的同源性而建立的 顺序 该提案的具体目标之一是建立 这种蛋白质具有酪氨酸激酶活性。 实验 被设计用来检测自身磷酸化， 其他底物的磷酸化。 第二个具体目标是审查 hck蛋白。 基于我们对与 酪氨酸激酶，我们提出了一系列的实验， 研究hck在转化，生长或 激活巨噬细胞。 使用的结构 分别表达hck的正义或反义RNA， 在正常巨噬细胞中表达或阻断hck的表达， 选择的巨噬细胞样细胞系。 如果我们能证明 hck能够转化细胞，这种酪氨酸激酶可能作为 未来研究转型的合适模式 造血谱系 该项目的长期目标是确定以下方面的作用： HCK在正常巨噬细胞功能中作用，并将该信息用作 一种可能调节巨噬细胞生长或功能的方法 在免疫反应中。 hck表达的相关性 与造血谱系细胞的结合可能被证明是一种 我们研究免疫调节的有趣模型 系统

The focus of this proposal is the tyrosine kinase, hck (hematopoietic cell kinase) expressed primarily in cells of the myloid lineage. Its relationship to the src family of tyrosine kinase is established based on homology at the level of DNA sequence. One of the specific aims in the proposal is to establish that this protein has tyrosine kinase activity. Experiments have been designed to test for autophosphorylation as well as phosphorylation of other substrates. The second specific aim is to examine possible functions of the hck protein. Based on our knowledge of functions associated with tyrosine kinases, we have proposed a series of experiments to examine the possible role of hck in the transformation, growth or activation of macrophages. Using constructions that either express sense or antisense RNA for hck we will respectively over express or block the expression of hck in normal macrophages or selected macrophage-like cell lines. If we can demonstrate that hck is able to transform cells, this tyrosine kinase may serve as a suitable model for future studies of transformation within the hematopoietic lineage. The long-term objectives of this project are to define the role of hck in normal macrophage function and to use this information as a means of possibly modulating macrophage growth or function within the immune response. The association of hck expression with cells in the hematopoietic lineage may prove to be an interesting model for our studies on the regulation of the immune system.