Wilkinson M G, Millar J B
Department of Molecular Neurobiology, SmithKline Beecham Pharmaceuticals Plc, New Frontiers Science Park, Harlow, Essex, CM19 5AW U.K.
FASEB J. 2000 Nov;14(14):2147-57. doi: 10.1096/fj.00-0102rev.
In an often rapidly changing environment, cells must adapt by monitoring and reacting quickly to extracellular stimuli detected by membrane-bound receptors and proteins. Reversible phosphorylation of intracellular regulatory proteins has emerged as a crucial mechanism effecting the transmission and modulation of such signals and is determined by the relative activities of protein kinases and phosphatases within the cell. These are often arranged into complex signaling networks that may function independently or be subject to cross-regulation. Recently, genetic and biochemical analyses have identified the universally conserved mitogen-activated protein (MAP) kinase cascade as one of the most ubiquitous signal transduction systems. This pathway is activated after a variety of cellular stimuli and regulates numerous physiological processes, particularly the cell division cycle. Progression through the cell cycle is critically dependent on the presence of environmental growth factors and stress stimuli, and failure to correctly integrate such signals into the cell cycle machinery can lead to the accumulation of genetic damage and genomic instability characteristic of cancer cells. Here we focus on the MAP kinase cascade and discuss the molecular mechanisms by which these extensively studied signaling pathways influence cell growth and proliferation.
在一个常常迅速变化的环境中，细胞必须通过监测并快速响应由膜结合受体和蛋白质检测到的细胞外刺激来实现适应。细胞内调节蛋白的可逆磷酸化已成为影响此类信号传递和调节的关键机制，并且由细胞内蛋白激酶和磷酸酶的相对活性决定。这些蛋白激酶和磷酸酶常常被组织成复杂的信号网络，这些网络可能独立发挥作用，也可能受到交叉调节。最近，遗传学和生物化学分析已确定普遍保守的丝裂原活化蛋白（MAP）激酶级联是最普遍存在的信号转导系统之一。该途径在多种细胞刺激后被激活，并调节众多生理过程，尤其是细胞分裂周期。细胞周期的进展严重依赖于环境生长因子和应激刺激的存在，未能将此类信号正确整合到细胞周期机制中会导致遗传损伤的积累以及癌细胞特有的基因组不稳定。在这里，我们聚焦于MAP激酶级联，并讨论这些经过广泛研究的信号通路影响细胞生长和增殖的分子机制。
