CHARACTERIZATION OF A SRC-RELATED GENE IN MACROPHAGES

这项提案的重点是酪氨酸激酶，HCK (造血细胞激活素)主要在细胞中表达 肉样血统。它与酪氨酸src家族的关系 在DNA水平上的同源性基础上建立了激酶 序列。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。实验已经 被设计用来测试自动磷酸化以及 其他底物的磷酸化。 第二个具体目标是检查 HCK蛋白。根据我们对以下功能的了解 酪氨酸激酶，我们提出了一系列实验来 研究HCK在转化、生长或 巨噬细胞的激活。使用符合以下条件的构造 我们将分别针对HCK表达正义或反义RNA 在正常巨噬细胞中表达或阻断HCK的表达 筛选出巨噬细胞样细胞系。如果我们能证明这一点 HCK能够转化细胞，这种酪氨酸激酶可能作为一种 适用于未来研究内部转化的模型 造血血统。 该项目的长期目标是确定 HCK在正常巨噬细胞功能中的作用并将这一信息用于 一种可能调节巨噬细胞生长或功能的手段 在免疫反应中。人绒毛膜促性腺激素释放酶表达的相关性 造血系中的细胞可能被证明是一种 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.