MN+2-PHOSPHOLIPID STIM PK AND LEUKEMIC DIFFERENTIATION

MN 2-磷脂刺激 PK 和白血病分化

• 批准号: 3183947
• 负责人: LAURENCE ELIAS
• 金额: $ 9.87万
• 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 1989-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3183947
• 关键词: cell differentiation; chemical structure function; enzyme induction /repression; enzyme substrate; gel electrophoresis; leukopoiesis; manganese; myelogenous leukemia; myeloid stem cell; ornithine decarboxylase; phospholipids; 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（Protein Kinase M，PKM）是新近发现的HL-60细胞中的一种蛋白激酶 早幼粒细胞性白血病细胞，其表现出受磷脂调节， 一个模式区从众所周知的钙磷脂依赖性 蛋白激酶（PKC）。 这项建议的重点是PKM在以下方面可能发挥的作用： 用化学试剂控制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 在正常和恶性细胞类型之间。 先前标识的 HL-60中PKM的内源性底物有待进一步表征， 与其他激酶的底物相比。 的可能性 PKM的内源性42 kDa底物是蛋白质合成的起始点 因子eIF-2是要探讨，因为是可能的关系，72 鸟氨酸脱羧酶的kDa底物。 PKM与 抑制PKM的视黄酸和其他可能的PKM调节剂， 生理学意义，将进一步表征为 结构-活性相关性和详细的测量， 纯化酶 进一步定义摄取和细胞内 HL-60细胞对视黄酸的处置也将继续进行，因为它 属于视黄酸与PKM的可能相互作用。 这些 因此，研究集中在一个新发现的详细特征 可能在控制人类白血病细胞中起作用的酶 分化