PROTEIN KINASE C IN CELL GROWTH AND DIFFERENTIATION

此续订申请的总体目标主要包括 分子、免疫学、药理学、调节性和 蛋白激酶C(PKC)在细胞生长和生长中的功能 差异化。活性水平、免疫反应性和 免疫细胞化学定位(在光和电子上 使用Anit-PKC抗血清对PKC进行微观水平的研究 PI‘s Lab与内源底物蛋白的磷酸化 对于HL60、K562、KG-1、KG-1a、CHO和E7SKS细胞中的PKC 审查，以使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 利用BHK-21及其温度敏感突变体进行 (在细胞周期的不同阶段被阻断)，以及BALB/c-3T3和 其转化的亚系(M-MSV、K-BALB和3T12-3)，从而 PKC系统在细胞周期进程和细胞中的作用 增长情况可以进一步调查。此外， 现有的抗癌药物和合成的类似物 烷基琥珀酰磷脂和磷脂酰胆碱对PKC活性和 蛋白激酶C定向转位、蛋白磷酸化与细胞 将检测TPA诱导的分化，以便PKC可以 被确立为这些代理人的潜在行动地点。它是 希望拟议的研究将产生新的知识 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。

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.