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. ***
