RUI: Induction of Cell Division by Protein Kinase C

[220108] Stith发现一种能诱导非洲爪蟾卵母细胞减数分裂的磷脂酯，提示了一条诱导减数分裂细胞分裂的新途径。众所周知，磷酸盐通过蛋白激酶C起作用，但不知道蛋白激酶C以外的细胞分裂途径。蛋白激酶C也被认为参与ras p21、胰岛素、胰岛素样生长因子-1 （IGF-1）和其他一些生长因子的增殖途径。由于磷脂、ras p21、胰岛素和IGF-1启动非洲爪蟾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细胞周期调节蛋白中的一种或多种起作用。通过体内和体外研究，ras p21, mos， cyclin和p34cdc2的磷酸化，数量和活性将作为蛋白激酶C活性的功能进行检查。我们可能会发现只有一种同工酶形式的PKC对增殖的调节起核心作用，PKC通过调节特定蛋白诱导细胞分裂。这项研究将阐明迄今为止尚未确定的细胞分裂途径的步骤。某些植物产物，佛酚酯，在动物细胞中诱导细胞分裂。这些化学物质会激活一种叫做蛋白激酶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来诱导细胞分裂。蛋白激酶C激活后导致细胞分裂的步骤尚不清楚。在过去的五年里，一个独立的研究方向是寻找对细胞分裂很重要的基因和蛋白质。其中一些新发现的蛋白质被称为mos， cyclin， p34cdc2和ras p21。本研究的目的是：(a)确定蛋白激酶C是否可以在试管或活细胞中将磷酸盐转移到这些蛋白质上，(b)如果可以，定位磷酸盐添加到这些蛋白质上的位置，(C)确定这些重要的细胞分裂蛋白是否通过添加磷酸盐而开启或关闭。这项研究的结果应该在导致生长因子诱导细胞分裂的事件序列中定义新的步骤。由于这项研究将在一所本科院校进行，并有学生参与，因此它也将有助于培养下一代科学家。＊＊＊

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. ***