CD45 IN CELL CYCLE & SIGNALING

细胞周期中的 CD45

• 批准号: 6258809
• 负责人: WALTER J ESSELMAN
• 金额: $ 0.09万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6258809
• 关键词: biological products; biomedical resource; drug adverse effect; enzymes; liver; proteins

CD45 is a receptor-type protein tyrosine phosphatase (PTP) which is ubiquitous and abundant in hematopoietic cells. The overall objective of this study is to delineate the role of CD45 phosphorylation in the regulation of cell division in normal and transformed cells. We previously reported that CD45 PTP activity is elevated in lymphocytes during G1 and G2/M. The temporal relationship of this elevation with the phosphorylation events occurring in the cell cycle suggests an important role for CD45 in the regulation of the phosphorylation state of membrane signaling elements. This study is designed to determine whether CD45 becomes activated during the cell cycle. The role of CD45 will be studied by separation of CTLL-2 cells into cell cycle stages by centrifugal elutriation, followed by detailed analysis of CD45 phosphorylation and PTP activity. The kinetics of cell cycle progression will be compared in CD45 positive and negative cells. The detailed phosphorylation sites of CD45 in cell cycle phases have been determined by phosphoamino acid analysis, by phosphopeptide mapping and by MALDI-MS. This approach has already led to the identification of six sites. Key phosphorylation sites are being modified by site directed mutagenesis to confirm their role in CD45 activity. Finally, the proteins and protein kinases which associate with CD45 cells will be identified. These studies are important to the understanding of phosphorylation events which regulate the cell cycle and the receptivity of cells to external signals, and will contribute to the understanding of the deregulation of the cell cycle often associated with neoplastic events and cancer.

CD45是一种受体型蛋白酪氨酸磷酸酶（PTP），该蛋白磷酸酶（PTP） 在造血细胞中无处不在且丰富。 总体 这项研究的目的是描述CD45的作用 在正常和 转化的细胞。 我们以前报道了CD45 PTP活性是 G1和G2/m期间淋巴细胞的升高。 时间关系 在此升高中，磷酸化事件发生在 细胞周期表明CD45在调节中的重要作用 膜信号元件的磷酸化状态。 这项研究 旨在确定CD45是否在 细胞周期。 CD45的作用将通过CTLL-2分离来研究 通过离心放大，进入细胞周期阶段，然后是 CD45磷酸化和PTP活性的详细分析。 这 CD45阳性将比较细胞周期进程的动力学 和负细胞。 CD45的详细磷酸化位点 细胞周期阶段已通过磷酸氨基酸分析确定， 通过磷酸肽映射和MALDI-MS。 这种方法已经 导致识别六个站点。 关键的磷酸化位点是 被定向诱变的站点修改以确认其在 CD45活性。 最后，蛋白质和蛋白激酶 将鉴定与CD45细胞的关联。 这些研究是 对理解磷酸化事件的理解很重要 调节细胞周期和细胞对外部的接受度 信号，并将有助于理解放松管制 细胞周期通常与肿瘤事件和癌症有关。