Protein kinase C-mediated bidirectional regulation of endothelial cell growth

在人脐静脉内皮细胞中，蛋白激酶C(PKC)在G1期的早期刺激导致生长因子刺激的DNA合成增强，cdc2和cdk2细胞周期蛋白依赖的激酶激活，cdc2、细胞周期蛋白A、d1和E的mRNA表达增加，而cdk2和cdk4不表达。相反，在G1期晚期，PKC的刺激完全抑制DNA合成、细胞周期蛋白依赖性蛋白激酶的激活以及除细胞周期蛋白D1外的同一组分子的mRNA表达。此外，我们发现PKC的刺激以双峰方式调节E2F1和B-MYB的信息水平，这两个转录因子参与控制哺乳动物细胞周期的进程。这些结果表明，PKC信号转导途径，取决于G1期的激活时间，对生长调节基因的信息水平进行正向或负向调节，这些基因对G1期到S期的进展至关重要。

In human umbilical vein endothelial cells, the protein kinase C (PKC) stimulation during the early G1 phase leads to potentiations in growth factor-stimulated DNA synthesis, the activation of cdc2 and cdk2 cyclin-dependent kinases, and the mRNA expression of cdc2, cyclins A,D1 and E,but not cdk2 or cdk4. Conversely, the PKC stimulation in the late G1 phase completely inhibits DNA synthesis, the activation of cyclin-dependent kinases, and the mRNA expression of the same set of molecules except cyclin D1. Further, we found that the PKC stimulation bimodally regulates the message levels of E2F1 and B-myb, which are transcription factors implicated in the control of the mammalian cell cycle progression. These results indicate that the PKC signal transduction pathway, depending on the timing of activation in the G1 phase, either positively or negatively regulates the message level of growth-regulating genes that are crucial for the G1 to S phase progression.