PKC AND THE SECRETION AND BIOSYNTHESIS OF NEUROPEPTIDES IN ATT-20 CELLS

PKC 与 ATT-20 细胞中神经肽的分泌和生物合成

• 批准号: 3821251
• 负责人: R ESKAY
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 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/3821251
• 关键词: cell membrane; cytoplasm; ethanol; membrane permeability; neoplastic cell culture for noncancer research; peptide hormone biosynthesis; phorbols; protein kinase C; tissue /cell culture

Enhanced protein phosphorylation is one of the intracellular events which invariably follows membrane receptor activation. Recently identified Protein Kinase C (PKC) is a unique enzyme which phosphorylates specific proteins, whose functions remain to be determine. PKC requires a phospholipid and a diacylglycerol (DAG) for maximal activity. DAG is the hydrolytic product of membrane polyphosphoinositide (PI) breakdown, which occurs following membrane receptor occupancy, and is one of the initial events in signal transduction. The release of FAG during PI turnover substantially stimulates PKC activity over that observed in quiescent cells. The known co-carcinogen or tumor promoter, 12-0-tetradecanoylphorbol 13-acetate (TPA) specifically increases membrane PKC activity. Associated with this increased membrane PKC activity is a reduction of cytosolic PKC activity, which suggest that translocation of PKC from the cytosol to the membrane is an important intracellular event. TPA treatment of AtT-20 cells resulted in a dose-related increase in BE secretion and translocation of PKC from the cytosolic to the membrane fraction. A maximally-stimulating concentration of TPA enhanced PKC activity 2-fold within 1 min and 5-fold within 3 min. Preincubation of AtT-20 cells with ethanol (0.1- 0.6%) for 24 hours resulted in a dose-related 2-5 fold reduction in cytosolic PKC activity and a 50% reduction in membrane PKC activity at .0.4% ethanol. Ethanol pretreatment for 24 hours only marginally reduced the ability of a maximal stimulatory concentration of TPA to induce translocation of PKC.

蛋白磷酸化增强是细胞内的一种 在膜受体激活之后发生的事件。 最近发现的蛋白激酶C(PKC)是一种独特的酶 它使特定的蛋白质磷酸化，其功能仍然是 心意坚定。PKC需要一个磷脂和一个二酰甘油 (DAG)以获得最大活动。DAG是水解物 膜多磷肌醇(PI)分解，发生 继膜受体占据之后，也是最早的 信号转导中的事件。猪繁殖过程中烟雾剂的释放 营业额大幅刺激PKC活动超过观察到的 在静止的牢房里。已知的致癌物或肿瘤促进剂， 12-0-十四酰佛波醇13-乙酸酯(TPA)特别增加 膜PKC活性。与此相关的增加 膜PKC活性是胞质PKC活性的降低， 这表明PKC从胞浆转位到胞浆 膜是一种重要的细胞内事件。 TPA对AtT-20细胞的作用呈剂量依赖性增加 在BE的分泌和PKC从胞浆到胞浆的移位中 膜组分。极具刺激性的注意力 TPA在1分钟内将PKC活性提高2倍，将PKC活性提高5倍 在3分钟内。乙醇对AtT-20细胞的预孵育作用 0.6%)持续24小时，与剂量相关的减少2-5倍 胞质PKC活性和膜PKC活性降低50% 活性为.0.4%乙醇。仅限24小时的乙醇预处理 略微降低了最大刺激的能力 TPA浓度可诱导PKC易位。