MN+2-PHOSPHOLIPID STIM PK AND LEUKEMIC DIFFERENTIATION

MN 2-磷脂刺激 PK 和白血病分化

• 批准号: 3183950
• 负责人: LAURENCE ELIAS
• 金额: $ 5.98万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-05-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3183950
• 关键词: cell differentiation; chemical structure function; enzyme induction /repression; enzyme inhibitors; enzyme mechanism; enzyme substrate; gel electrophoresis; leukopoiesis; manganese; myelogenous leukemia; myeloid stem cell; ornithine decarboxylase; phospholipids; protein biosynthesis; protein kinase; retinoate; tissue /cell culture

Protein Kinase M (PKM) is a recently discovered protein kinase from HL-60 promyelocytic leukemic cells which exhibits modulation by phospholioids in a pattern district from the well known calcium-phospholipid dependent protein kinase (PKC). This proposal focuses upon PKM's possible role in the control of HL-60 proliferation and differentiation by chemical agents, especially retinoic acid. Purification and further basic biochemical characterization of PKM is planned, as well as study of PKM's distribution among normal and malignant cell types. The previously identified endogenous substrates of PKM in HL-60 are to be further characterized and compared to substrates of other kinases. The possibility that the endogenous 42 kDa substrate of PKM is the protein synthesis initiation factor eIF-2 is to be explored, as is the possible relationship to the 72 kDa substrate to ornithine decarboxylase. The interaction of PKM with retinoic acid, which inhibits PKM, and other possible modulators of physiologic significance, is to be further characterized by structure-activity correlation and by detailed measurements upon the purified enzyme. Further definition of the uptake and intracellular disposition of retinoic acid by HL-60 cells is also to be pursued as it pertains to the possible interaction of retinoic acid with PKM. These studies thus focus upon the detailed characterization of a newly discovered enzyme which may have a role in the control of human leukemic cellular differentiation.

蛋白激酶 M (PKM) 是最近从 HL-60 中发现的一种蛋白激酶 早幼粒细胞白血病细胞在 来自众所周知的钙磷脂依赖性的模式区 蛋白激酶（PKC）。 该提案重点关注 PKM 在以下方面可能发挥的作用： 通过化学试剂控制HL-60增殖和分化， 尤其是视黄酸。 纯化和进一步的基础生化 计划对 PKM 进行表征，并研究 PKM 的分布 正常和恶性细胞类型之间。 先前确定的 HL-60 中 PKM 的内源底物有待进一步表征和 与其他激酶的底物相比。 的可能性是 PKM 的内源 42 kDa 底物是蛋白质合成的起始点 第 72 章 鸟氨酸脱羧酶的 kDa 底物。 PKM 的相互作用 视黄酸，可抑制 PKM，以及其他可能的调节剂 生理意义，有待进一步表征 结构-活性相关性和通过详细测量 纯化的酶。 摄取和细胞内的进一步定义 HL-60 细胞对视黄酸的处置也有待研究，因为它 涉及视黄酸与 PKM 可能的相互作用。 这些 因此，研究的重点是新发现的详细特征 可能在控制人类白血病细胞中发挥作用的酶 差异化。