OXIDASE-RELATED 48K PHOSPHOPROTEIN OF HUMAN NEUTROPHILS

人中性粒细胞的激活伴随着磷酸化 一种48K磷蛋白。 48K磷蛋白和 呼吸爆发氧化酶激活的过程是由 观察到这种蛋白质的磷酸化在两种情况下是有缺陷的， 慢性肉芽肿病的形式，一组遗传性疾病 其中呼吸爆发氧化酶不能发挥作用。 我们建议 在分子方面表征48K磷蛋白， 它与其他氧化酶组分的相互作用。 单克隆和多克隆 将获得抗48K磷蛋白的抗体并用作 用于分离和测序所述蛋白质的cDNA克隆的探针。 一旦 这个克隆是可用的，它将被用作探针来研究 蛋白质的染色体定位以及其在 吞噬细胞 将进行研究，以确定 48K磷蛋白的各种异构体上的磷酸基团。 的 磷蛋白将被纯化和结晶， 确定其三维结构。 最后，我们将研究 48K磷蛋白与其他氧化酶组分的相互作用， 用去污剂激活无细胞系统中的氧化酶。

The activation of human neutrophils is accompanied by the phosphorylation of a 48K phosphoprotein. A connection between the 48K phosphoprotein and the process of respiratory burst oxidase activation is suggested by the observations that the phosphorylation of this protein is defective in two forms of chronic granulomatous disease, a group of inherited conditions in which the respiratory burst oxidase fails to function. We propose to characterize the 48K phosphoprotein in molecular terms and in terms of its interaction with other oxidase components. Monoclonal and polyclonal antibodies against the 48K phosphoprotein will be obtained and used as probes for isolating and sequencing a cDNA clone of the protein. Once this clone is available, it will be used as a probe to study the chromosomal location of the protein as well as its expression in phagocytes. Studies will be carried out to define number and location of phosphate groups on the various isoforms of the 48K phosphoprotein. The phosphoprotein will be purified and crystallized for purposes of determining its 3-dimensional structure. Finally, we will examine interactions of the 48K phosphoprotein with other oxidase components and with detergents that activate the oxidase in the cell-free system.