STUDIES ON THE NATURE AND FUNCTION OF THE PHOSPHOPROTEIN, PROSOLIN

磷酸蛋白普罗索林的性质和功能研究

• 批准号: 3808555
• 负责人: H L COOPER
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3808555
• 关键词: DNA replication; T lymphocyte; cell differentiation; cellular oncology; cytoskeletal proteins; growth inhibitors; hematopoietic stem cells; human tissue; lymphocyte; lymphocyte proliferation; molecular cloning; myelogenous leukemia; neoplastic cell; nucleic acid sequence; phosphoproteins; phosphorylation; protein biosynthesis; protein kinase; protein sequence; protein structure function; tissue /cell culture

We have continued our studies on the cytosolic phosphoprotein, Prosolin, which was discovered in this laboratory. It is a major cytosolic protein of proliferating human lymphocytes and promyelocytic cells, but is not expressed in resting peripheral blood lymphocytes. We found that prosolin is an important early target of the activities associated with T-cell receptor (TCr) activation, indicating that prosolin phosphorylation serves to transmit the signal generated by TCr occupancy in the proliferating normal lymphocyte. Prosolin phosphorylation induced by TCr activation or by other treatments is invariably followed by rapid, but temporary, down regulation of DNA synthesis in normal proliferating lymphocytes. This may represent a normal regulatory aspect of the immune system. The rapid phosphorylation of prosolin that follows TCr activation is complex, resulting in 4 phosphorylated forms of the molecule containing variable numbers of phosphorylated serine residues. Evidence suggests that more than one protein kinase is involved in this complex phosphorylation event, and that one of these activities may be deficient in T-cell leukemia cells with the result that some of the phosphorylated forms of prosolin do not appear in such cells. We have cloned and sequenced the prosolin cDNA from normal human peripheral blood lymphocytes and have identified various potential phosphorylation sites.

我们继续对胞浆磷蛋白Prosolin进行研究， 它是在这个实验室里发现的。它是一种主要的胞质蛋白 增殖的人类淋巴细胞和早幼粒细胞，但不是 在静息状态的外周血淋巴细胞中表达。我们发现 Prosolin是与以下相关的活动的重要早期靶点 T细胞受体(TCR)激活，表明前列腺素 磷酸化用于传递TCR占用产生的信号 在增殖的正常淋巴细胞中。Prosolin诱导的磷酸化 通过TCR激活或通过其他处理总是紧跟着快速， 但在正常增殖中，DNA合成的暂时性下调 淋巴细胞。这可能代表了免疫的正常调节方面。 系统。前列腺素在TCR之后的快速磷酸化 激活是复杂的，导致4种磷酸化形式的 含有数量可变的磷酸化丝氨酸残基的分子。 有证据表明不止一种蛋白激酶参与了这一过程。 复杂的磷酸化事件，并且这些活性之一可能是 缺乏T细胞白血病细胞，结果是一些 磷酸化形式的前列腺素不会出现在这样的细胞中。我们有 正常人外周血中前列腺素基因的克隆及序列分析 并已确定了各种潜在的磷酸化位点。