MN+2-PHOSPHOLIPID STIM PK AND LEUKEMIC DIFFERENTIATION

MN 2-磷脂刺激 PK 和白血病分化

• 批准号: 3183954
• 负责人: LAURENCE ELIAS
• 金额: $ 8.95万
• 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/3183954
• 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(PKM)是新近发现的一种来自HL-60的蛋白激酶 磷脂对早幼粒细胞白血病细胞的调节作用 众所周知的钙-磷脂依赖的图案区 蛋白激酶(PKC)。本提案侧重于PKM在以下方面可能发挥的作用 化学药物对HL-60细胞增殖分化的调控作用 尤其是维甲酸。提纯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中。先前确定的 HL-60细胞中PKM的内源性底物有待进一步鉴定和鉴定 与其他酶的底物相比。有没有可能 PKM内源42 kDa底物是蛋白质合成的起点 因子EIF-2有待探索，与72的可能关系也是如此 KDA底物为鸟氨酸脱羧酶。PKM与互联网的相互作用 维甲酸，它抑制PKM，以及其他可能的调节剂 生理意义，是要进一步刻画 通过对结构-活性相关性的详细测量， 纯化的酶。对摄取和细胞内摄取的进一步定义 HL-60细胞对维甲酸的处置也是值得研究的问题。 与维甲酸与PKM可能的相互作用有关。这些 因此，研究集中在对一种新发现的 可能在控制人类白血病细胞中发挥作用的酶 差异化。