PROTEIN KINASE C IN CELL GROWTH AND DIFFERENTIATION

细胞生长和分化中的蛋白激酶 C

• 批准号: 3174352
• 负责人: JYH-FA KUO
• 金额: $ 17.34万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3174352
• 关键词: 3T3 cells; antineoplastics; cancer prevention; cell differentiation; cell growth regulation; cell population study; chromosome translocation; drug metabolism; electron microscopy; histochemistry /cytochemistry; immunochemistry; immunocytochemistry; leukemia; lysophospholipids; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer pharmacology; neoplasm /cancer therapy; neoplastic cell; phosphatidylcholines; phosphoproteins; phosphorylation; protein kinase C; temperature sensitive mutant

The overall goals of this renewal application cover primarily the molecular, immunological, pharmacological, regulatory and functional aspects of protein kinase C (PKC) in cell growth and differentiation. The activity level, immunoreactivity and immunocytochemical localization (both at the light and electron microscopic level of PKC, using anit-PKC antisera developed in the PI's lab, and phosphorylation of endogenous substrate proteins for PKC in HL60, K562, KG-1, KG-1a, CHO and E7SKS cells will be examined, so that the role of the PKC system in the TPA- induced cell differentiation can be assessed. Similar studies will be conducted using BHK-21 and its temperature sensitive mutants (blocked at different phases of cell cycle), and BALB/c-3T3 and its transformed sublines (M-MSV, K-BALB and 3T12-3), so that the role of the PKC system in cell cycle progression and cell growth can be further investigated. In addition, the effects of existing anti-cancer agents and synthetic analogs of alkyllsophospholipid and phosphatidylcholine on PKC activity and directional PKC translocaton, protein phosphorylation and cell differentiation induced by TPA will be examined, so that PKC can be established as a potential site of actions of these agents. It is hoped that the proposed research would yield new knowledge regarding the regulation of cell growth and differentiation, which would potentially aid cancer prevention and therapy.

此更新应用程序的总体目标主要包括 分子、免疫学、药理学、调节和 蛋白激酶C（PKC）在细胞生长中的功能方面， 分化 活性水平、免疫反应性和 免疫细胞化学定位（光和电子 使用抗-PKC抗血清， PI的实验室和内源性底物蛋白的磷酸化 对于HL 60、K562、KG-1、KG-1a、CHO和E7 SKS细胞中的PKC， 研究PKC系统在TPA中的作用- 可以评估诱导的细胞分化。 类似的研究将 使用BHK-21及其温度敏感突变体进行 （在细胞周期的不同阶段阻断），以及BALB/c-3 T3和 其转化的亚系（M-MSV、K-BALB和3 T12 -3），因此， PKC系统在细胞周期进程和细胞凋亡中的作用 可以进一步研究增长。 此外， 现有的抗癌剂及其合成类似物 磷脂酰胆碱对PKC活性的影响， PKC定向转位、蛋白磷酸化与细胞 将检查TPA诱导的分化，以便PKC可以 被确定为这些药剂的潜在作用部位。 是 希望这项研究能产生新的知识， 关于细胞生长和分化的调节， 可能有助于癌症的预防和治疗。

项目成果

Identification of specific sites in human P-glycoprotein phosphorylated by protein kinase C.

蛋白激酶 C 磷酸化人 P-糖蛋白中特定位点的鉴定。

• 发表时间: 1993
• 期刊: The Journal of biological chemistry
• 作者: Chambers,TC;Pohl,J;Raynor,RL;Kuo,JF
• 通讯作者: Kuo,JF

Multidrug-resistant human KB carcinoma cells are highly resistant to the protein phosphatase inhibitors okadaic acid and calyculin A. Analysis of potential mechanisms involved in toxin resistance.

多重耐药人 KB 癌细胞对蛋白磷酸酶抑制剂冈田酸和花萼蛋白 A 具有高度耐药性。分析毒素耐药性的潜在机制。

• DOI: 10.1002/ijc.2910530225
• 发表时间: 1993
• 期刊: International journal of cancer
• 影响因子: 6.4
• 作者: Chambers,TC;Raynor,RL;Kuo,JF
• 通讯作者: Kuo,JF