PKC-DELTA IN HEMATOPOIETIC CELL DIFFERENTIATION PATHWAY

造血细胞分化途径中的 PKC-Delta

• 批准号: 3752788
• 负责人: J H PIERCE
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3752788
• 关键词: Baculoviridae; biological signal transduction; cell differentiation; enzyme activity; growth factor receptors; hematopoiesis; hematopoietic stem cells; insulin receptor; intracellular transport; macrophage; monocyte; myeloid stem cell; phorbols; phosphorylation; platelet derived growth factor; protein kinase C; protein transport; protein tyrosine kinase; transfection; tyrosine

Protein kinase C (PKC) plays a very important role in cell growth and differentiation. Recent work has demonstrated that among several PKC isoforms investigated. only PKC-alpha and PKC-delta were able to induce 32D cell monocytic differentiation when they were overexpressed in 32D cells and activated by 12-0-tetradecanoyl-phorbol-I3-acetat (TPA). In order to elucidate the possible mechanism of PKC-alpha- and PKC-delta- induced monocytic differentiation. analysis of whether TPA stimulation resulted in tyrosine phosphorylation of cellular substrate(s) in the 32D/PKC-alpha and 32D/PKC-delta transfectants was investigated. Results demonstrated that PKC-delta itself was tyrosine phosphorylated in response to TPA stimulation. Tyrosine phosphorylation of PKC-delta was observed during the entire TPA-induced 32D/PKC-delta cell differentiation period. It also occurred when baculovirus-derived PKC-delta was incubated in vitro with platelet-derived growth factor (PDGF)-beta-R. insulin receptor or a nonreceptor tyrosine kinase, fyn. PKC-delta activity after tyrosine phosphorylation in vitro was increased towards its substrate. Cotransfection of PKC-delta and PDGF-beta-R in 32D cells (32D/PDGF-beta-R/PKC-delta) provided evidence that PKC-delta was translocated from the cytosol to the membrane. and tyrosine phosphorylated in the membrane when the cells were stimulated with PDGF- BB. PKC-delta activity was also increased in the membrane fraction. indicating the positive correlation between PKC-delta tyrosine phosphorylation and its activation in vivo. 32D/PDGF-beta-R/PKC-delta cells differentiated toward macrophages when they were exposed to PDGF-BB overnight. whereas PDGF-BB treatment of 32D cells transfected with PDGF- beta-R alone resulted in very slight differentiation. These results suggest that PKC-delta plays a very important role in myeloid differentiatiOn when it is activated by TPA or by a reconstituted PDGF- beta-R signaling pathway.

蛋白激酶C （PKC）在细胞生长和发育过程中起着非常重要的作用