RUI: Induction of Cell Division by Protein Kinase C

RUI：蛋白激酶 C 诱导细胞分裂

• 批准号: 9220108
• 负责人: Bradley Stith
• 金额: $ 31.28万
• 依托单位: University of Colorado at Denver-Downtown Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1997-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9220108&HistoricalAwards=false
• 关键词: RUI; Induction; Cell; Division; Protein

9220108 Stith A new pathway for the induction of meiotic cell division was suggested when a phorbol ester was found to induce meiosis in Xenopus oocytes. It is known that phorbols act through protein kinase C, but the pathway to cell division beyond protein kinase C is not known. Protein kinase C is also believed to be involved in the proliferative pathway of ras p21, insulin, insulin-like growth factor-1 (IGF-1) and some other growth factors. Since phorbols, ras p21, insulin and IGF-1 initiate meiotic cell division in Xenopus laevis oocytes, we will examine whether PKC acts through regulation of one or more of four different cell cycle regulatory proteins. With both in vivo and in vitro studies, the phosphorylation, amount and activity of ras p21, mos, cyclin, and p34cdc2 will be examined as a function of protein kinase C activity. It may be found that only one isozymic form of PKC is central to the regulation of proliferation and that PKC induces cell division through regulation of specific protein(s). This research should elucidate heretofore uncharacterized steps in the pathway to cell division. %%% Certain plant products, phorbol esters, induce cell division in animal cells. These chemicals activate an enzyme known as protein kinase C (PKC). The function of protein kinase C is to transfer phosphate groups onto other proteins. Much evidence suggests that growth hormones such as insulin, insulin-like growth factor 1 and epidermal growth factor induce cell division by activating protein kinase C. The steps beyond activation of protein kinase C which lead to cell division are not known. A separate line of research over the past five years has been the search for genes and proteins important to cell division. Some of the newly discovered proteins are called mos, cyclin, p34cdc2 and ras p21. The goals of this research are: (a) to determine whether protein kinase C can transfer phosphate to these proteins in a test tube or in living cells, (b) if i t does, to locate the site of phosphate addition to these proteins, and (c) determine whether these important cell division proteins are turned on or off by the addition of phosphate. The results of this research should define new steps in the sequence of events that leads to induction of cell division by growth factors. Since this research will be carried out at an undergraduate institution with the participation of students, it will also contribute to training a future generation of scientists. ***

9220108当发现佛波酯诱导非洲爪哇卵母细胞减数分裂时，提出了一种新的诱导减数分裂的途径。已知佛波醇通过蛋白激酶C发挥作用，但除了蛋白激酶C之外，细胞分裂的途径尚不清楚。蛋白激酶C也被认为参与了ras p21、胰岛素、胰岛素样生长因子-1和其他一些生长因子的增殖途径。由于佛波醇、rasp21、胰岛素和IGF-1启动了非洲爪哇卵母细胞的减数分裂，我们将研究PKC是否通过调节四种不同的细胞周期调节蛋白中的一种或多种来发挥作用。通过在体内和体外的研究，将检测ras p21、mos、细胞周期蛋白和p34cdc2的磷酸化、数量和活性作为蛋白激酶C活性的函数。人们可能发现，只有一种同工酶形式的蛋白激酶C是中心的调控增殖和蛋白激酶C诱导细胞分裂通过调节特定的蛋白质(S)。这项研究应该阐明迄今为止尚未确定的细胞分裂途径的步骤。某些植物产品，佛波酯，能诱导动物细胞分裂。这些化学物质激活一种名为蛋白激酶C(PKC)的酶。蛋白激酶C的功能是将磷酸基团转移到其他蛋白质上。许多证据表明，胰岛素、胰岛素样生长因子1和表皮生长因子等生长激素通过激活蛋白激酶C诱导细胞分裂，而蛋白激酶C激活以外的步骤导致细胞分裂尚不清楚。过去五年的另一项研究是寻找对细胞分裂至关重要的基因和蛋白质。一些新发现的蛋白质被称为mos、细胞周期蛋白、p34cdc2和ras p21。这项研究的目的是：(A)确定蛋白激酶C是否能在试管中或在活细胞中将磷酸盐转移到这些蛋白质上；(B)如果可以，确定这些蛋白质中磷酸盐加成的位置；以及(C)确定这些重要的细胞分裂蛋白是否被磷酸盐加成打开或关闭。这项研究的结果应该确定导致生长因子诱导细胞分裂的事件序列中的新步骤。由于这项研究将在有学生参与的本科生机构进行，它也将有助于培养下一代科学家。***