Mittnacht S
Department of Cell and Molecular Biology, Institute of Cancer Research, London, UK.
Curr Opin Genet Dev. 1998 Feb;8(1):21-7. doi: 10.1016/s0959-437x(98)80057-9.
Two opposing enzymatic reactions control the activity of the retinoblastoma tumour suppressor protein, pRB. Phosphorylation inactivates pRB's ability to sequester miscellaneous cellular proteins, mostly involved in regulating gene transcription, whereas pRB dephosphorylation restores this ability. For some time now it has been suspected that members of the cyclin/cyclin-dependent kinase (cyclin/cdk) family mediate pRB inactivation. Recent results indicate that pRB phosphorylation is not executed by single kinase but by a combination of cyclin/cdks, each one phosphorylating a subset of pRB's phosphorylation sites. The different kinases appear to be activated by growth factors through distinct signal transduction pathways. This lends itself to an attractive model whereby pRB phosphorylation may constitute an integration point for these signalling pathways, perhaps allowing cell cycle progression only when concurrent activation of these signalling pathways has been achieved.
两种相反的酶促反应控制着视网膜母细胞瘤肿瘤抑制蛋白pRB的活性。磷酸化会使pRB隔离多种细胞蛋白（主要参与调节基因转录）的能力失活，而pRB去磷酸化则可恢复这种能力。一段时间以来，人们一直怀疑细胞周期蛋白/细胞周期蛋白依赖性激酶（cyclin/cdk）家族的成员介导pRB失活。最近的结果表明，pRB磷酸化并非由单一激酶执行，而是由细胞周期蛋白/cdks的组合完成，每种激酶磷酸化pRB磷酸化位点的一个子集。不同的激酶似乎通过不同的信号转导途径被生长因子激活。这就产生了一个有吸引力的模型，即pRB磷酸化可能构成这些信号通路的整合点，也许只有在这些信号通路同时被激活时才允许细胞周期进展。
