MN+2-PHOSPHOLIPID STIM PK AND LEUKEMIC DIFFERENTIATION

MN 2-磷脂刺激 PK 和白血病分化

• 批准号: 3183955
• 负责人: LAURENCE ELIAS
• 金额: $ 8.85万
• 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/3183955
• 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 （Protein Kinase M， PKM）是最近从HL-60中发现的一种蛋白激酶