The retinoblastoma protein is linked to the activation of Ras.
The retinoblastoma protein is linked to the activation of Ras.
复制标题
视网膜母细胞瘤蛋白与 Ras 的激活有关。
DOI：
10.1128/mcb.19.11.7724
复制
发表时间：
1999
影响因子：
5.3
通讯作者：
Ewen,ME
中科院分区：
文献类型：
--
作者：
Lee,KY;Ladha,MH;McMahon,C;Ewen,ME
内膜结合蛋白Ras整合各种细胞外信号，这些信号随后通过Raf/MEK/MAPK级联从细胞质传递到细胞核。在这里，我们表明，视网膜母细胞瘤蛋白pRb，以前报道的是该途径的核靶点，可以反过来影响Ras的激活状态。Rb缺陷的成纤维细胞显示升高水平（高达30倍）的激活Ras在G1期。表达野生型pRb或一些pRb突变体缺陷的E2 F调节逆转这种效果。我们提供的证据表明，中期G1激活Ras inRb缺陷细胞，发生在鸟嘌呤核苷酸结合的水平，不同于表皮生长因子诱导的刺激Ras，依赖于蛋白质合成。与pRb缺失相关的Ras活性水平异常可能是Rb缺陷细胞分化缺陷的原因，因为Rb −/−成纤维细胞中Ras活性的抑制恢复了MyoD的反式激活功能和骨骼肌分化晚期标志物的表达。这些数据表明，pRb和Ras之间的核质通讯是双向的。
The inner membrane-bound protein Ras integrates various extracellular signals that are subsequently communicated from the cytoplasm to the nucleus via the Raf/MEK/MAPK cascade. Here we show that the retinoblastoma protein pRb, previously reported to be a nuclear target of this pathway, can in turn influence the activation state of Ras.Rb-deficient fibroblasts display elevated levels (up to 30-fold) of activated Ras during G1. Expression of wild-type pRb or a number of pRb mutants defective in E2F regulation reverses this effect. We provide evidence that the mid-G1activation of Ras inRb-deficient cells, which occurs at the level of guanine nucleotide binding, differs from that of epidermal growth factor-induced stimulation of Ras, being dependent on protein synthesis. The aberrant levels of Ras activity associated with loss of pRb may be responsible for the differentiation defects inRb-deficient cells, because suppression of Ras activity inRb−/−fibroblasts restores the transactivation function of MyoD and the expression of a late marker of skeletal muscle differentiation. These data suggest that nuclear-cytoplasmic communication between pRb and Ras is bidirectional.