Samanta A, Greene M I
Center for Receptor Biology, University of Pennsylvania, School of Medicine, Philadelphia 19104-6082, USA.
Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6582-6. doi: 10.1073/pnas.92.14.6582.
Some growth factors transduce positive growth signals, while others can act as growth inhibitors. Nuclear signaling events of previously quiescent cells stimulated with various growth factors have been studied by isolating the complexed chromatin-associated proteins and chromatin-associated proteins. Signals from the plasma membrane are integrated within the cells and quickly transduced to the nucleus. It is clear that several growth factors, such as epidermal growth factor, transforming growth factor alpha (but not transforming growth factor beta), and platelet-derived growth factor, utilize similar intracellular signaling biochemistries to modulate nucleosomal characteristics. The very rapid and consistent phosphorylation of nuclear p33, p54, and low molecular mass proteins in the range of 15-18 kDa after growth factor stimulation implies that there is a coordination and integration of the cellular signaling processes. Additionally, phosphorylation of p33 and some low molecular mass histones has been found to occur within 5 min of growth factor treatment and to reach a maximum by 30 min. In this study, we report that Neu receptor activating factor also utilizes the same signaling mechanism and causes p33 to become phosphorylated. In addition, both the tumor promoter okadaic acid (which inhibits protein phosphatases 1 and 2A) and phorbol ester (phorbol 12-tetradecanoate 13-acetate) stimulate phosphorylation of p33, p54, and low molecular mass histones. However, transforming growth factor beta, which is a growth inhibitor for fibroblasts, fails to increase p33 phosphorylation. In general, p33 phosphorylation patterns correspond to positive and negative mitogenic signal transduction. p33 isolated from the complexed chromatin-associated protein fraction appears to be a kinase, or tightly associated with a kinase, and shares antigenicity with the cell division cycle-dependent Cdk2 kinase as determined by antibody-dependent analysis. The rapid phosphorylation of nucleosomal proteins may influence sets of early genes needed for the induction and progression of the cell cycle.
一些生长因子传递正向生长信号，而其他一些则可作为生长抑制剂。通过分离与染色质相关的复合蛋白和染色质相关蛋白，对用各种生长因子刺激的先前静止细胞的核信号事件进行了研究。来自质膜的信号在细胞内整合并迅速传递至细胞核。很明显，几种生长因子，如表皮生长因子、转化生长因子α（而非转化生长因子β）和血小板衍生生长因子，利用相似的细胞内信号生物化学来调节核小体特征。生长因子刺激后，核内p33、p54以及15 - 18 kDa范围内的低分子量蛋白非常迅速且一致地发生磷酸化，这意味着细胞信号转导过程存在协调与整合。此外，已发现p33和一些低分子量组蛋白在生长因子处理后5分钟内发生磷酸化，并在30分钟时达到最大值。在本研究中，我们报告Neu受体激活因子也利用相同的信号机制并导致p33磷酸化。此外，肿瘤启动子冈田酸（抑制蛋白磷酸酶1和2A）和佛波酯（佛波醇12 - 十四烷酸酯13 - 乙酸酯）均刺激p33、p54和低分子量组蛋白的磷酸化。然而，作为成纤维细胞生长抑制剂的转化生长因子β未能增加p33磷酸化。一般来说，p33磷酸化模式与正向和负向有丝分裂信号转导相对应。从与染色质相关的复合蛋白组分中分离出的p33似乎是一种激酶，或与一种激酶紧密相关，并且通过抗体依赖性分析确定其与细胞分裂周期依赖性Cdk2激酶具有抗原性。核小体蛋白的快速磷酸化可能会影响细胞周期诱导和进展所需的早期基因集。
