Control of the eukaryotic cell cycle by MAP kinase signaling pathways
Control of the eukaryotic cell cycle by MAP kinase signaling pathways
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DOI：
10.1096/fj.00-0102rev
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发表时间：
2000-11
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影响因子：
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通讯作者：
M. Wilkinson;J. Millar
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文献类型：
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作者：
M. Wilkinson;J. Millar
摘要在一个经常快速变化的环境中，细胞必须通过监测和快速反应膜结合受体和蛋白质检测到的细胞外刺激来适应。细胞内调节蛋白的可逆磷酸化已经成为影响这些信号的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。这些通常被安排成复杂的信号网络，可以独立运作或受到交叉调节。最近，遗传学和生物化学分析已经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。该途径在各种细胞刺激后被激活，并调节许多生理过程，特别是细胞分裂周期。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，并且未能将这些信号正确整合到细胞周期机制中可能导致癌细胞特有的遗传损伤和基因组不稳定性的积累。在这里，我们专注于MAP激酶级联，并讨论这些广泛研究的信号通路影响细胞生长和增殖的分子机制。威尔金森，M. G.，Millar，J. B. A. MAP激酶信号通路对真核细胞周期的调控。FASEB J. 14，2147 - 2157（2000）
ABSTRACT 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.—Wilkinson, M. G., Millar, J. B. A. Control of the eukaryotic cell cycle by MAP kinase signaling pathways. FASEB J. 14, 2147‐2157 (2000)