Livneh E, Shimon T, Bechor E, Doki Y, Schieren I, Weinstein I B
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Oncogene. 1996 Apr 4;12(7):1545-55.
Protein kinase C encodes a family of enzymes implicated in cellular differentiation, growth control and tumor promotion. However, very little is known with respect to the molecular mechanisms that link protein kinase C to cell cycle control. Here we report that ectopic expression of PKC eta in NIH3T3 fibroblasts blocks the normal phosphorylation of the Rb protein in quiescent cultures restimulated to enter the cell cycle; PKC eta activates a cellular program that includes increased expression of cyclins E (but not cyclin D), as well as the induced expression of the cyclin-dependent kinase inhibitors p21WAF1 and p27KIP1. The increased expression of the latter inhibitors and their association with the cyclin E-Cdk2 complex results in decreased cyclin E associated kinase activity. Furthermore, in contrast to the control NIH3T3 cells, the cell that express PKC eta can be induced to undergo adipocyte differentiation in response to adipogenic hormones. Thus, PKC eta induces altered expression of several cell cycle related functions, which may contribute to its ability to promote cellular differentiation.
蛋白激酶C编码一族与细胞分化、生长控制及肿瘤促进相关的酶。然而，关于将蛋白激酶C与细胞周期控制联系起来的分子机制，人们所知甚少。在此我们报告，在重新刺激进入细胞周期的静止培养的NIH3T3成纤维细胞中，PKC η的异位表达会阻断Rb蛋白的正常磷酸化；PKC η激活一个细胞程序，该程序包括细胞周期蛋白E（而非细胞周期蛋白D）表达增加，以及细胞周期蛋白依赖性激酶抑制剂p21WAF1和p27KIP1的诱导表达。后一种抑制剂表达的增加及其与细胞周期蛋白E-Cdk2复合物的结合导致细胞周期蛋白E相关激酶活性降低。此外，与对照NIH3T3细胞相反，表达PKC η的细胞可被诱导响应脂肪生成激素而进行脂肪细胞分化。因此，PKC η诱导几种细胞周期相关功能的表达改变，这可能有助于其促进细胞分化的能力。
