REGULATION OF THE ABL TYROSINE KINASE INHIBITOR PAG

描述（由申请人提供）：本计划的长期目标是 探讨Abl酪氨酸相互作用的意义和机制 我们用Pag基因敲除小鼠。Abl是非受体 酪氨酸激酶，在过去的二十年里一直在研究， 但其功能仍不清楚。它参与细胞周期，细胞 生长和凋亡将Abl与致癌途径联系起来。Pag是一种蛋白质， 抗氧化活性被自由基激活，并抑制激酶 研究的一部分将侧重于确定 Abl和Pag的相互作用位点，以及自由基对这种相互作用的调节 根的此外，我们还将重点介绍Pag的生理作用。这些 将在分离自Pag -/-小鼠的鼠胚胎成纤维细胞（MEF）中进行研究 在Pag -/-小鼠中也是如此。

DESCRIPTION (provided by applicant): The long term goal of this prosal is to study the significance and mechanism of the interaction of the Abl tyrosine kinase with Pag, for which we created a knock-out mouse. Abl is a non-receptor tyrosine kinase which has been studied now for over the past two decades, and yet its function is still not understood. Its involvement in cell cycle, cell growth and apoptosis links Abl to oncogenetic pathways. Pag, a protein with antioxidant actvity is activated by free radicals, and is inhibiting the kinase activity of Abl. One part of the study will focus on determination of the interactionsites of Abl and Pag, and the regulation of this interaction by free radicals. Additionally, we will focus on the physiological role of Pag. These studies will be done in murine embryo fibroblasts (MEFs) isolated from Pag -/-mice and in the Pag -/- mice.