The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition.
|核心內(nèi)容：
RAS依賴的細(xì)胞外信號調(diào)節(jié)激酶(ERK)1/2絲裂原活化蛋白(MAP)激酶通路在細(xì)胞增殖調(diào)控中起著核心作用。 在正常細(xì)胞中，ERK1/ERK2的持續(xù)激活是G1期向S期發(fā)展所必需的，并與細(xì)胞周期正調(diào)控因子的誘導(dǎo)和抗增殖基因的失活有關(guān)。 在表達(dá)活化的RAS或Raf突變體的細(xì)胞中，ERK1/2通路的過度激活通過誘導(dǎo)細(xì)胞周期蛋白依賴性激酶抑制劑的積聚而導(dǎo)致細(xì)胞周期停滯。 本文就激活的ERK1/ERK2調(diào)控哺乳動(dòng)物體細(xì)胞生長和細(xì)胞周期進(jìn)程的機(jī)制作一綜述。 The cell division cycle is the sequence of events by which cells faithfully replicate their DNA and then segregate the duplicated chromosomal DNA equally between two daughter cells. An intricate network of regulatory pathways ensures that each cell cycle event is performed correctly and in proper sequence (Morgan, 2007).
intricate ：to describe something that has many small parts or details.
The decision of cells to replicate their genetic material and divide is made in G1 and is influenced by extracellular signals (nutrients, mitogens, cytostatic factors, extracellular matrix). Once cells make their decision, they are irreversibly committed to complete the cycle independently of mitogenic factors. One of the key signal transduction pathways responsible for integrating these environmental signals and relaying the information to the cell cycle control system is the Ras-dependent extracellular signal-regulated kinase 1 (ERK1)/2 mitogenactivated protein (MAP) kinase pathway. MAP kinase pathways are evolutionarily conserved signaling modules by which cells transduce extracellular signals into intracellular responses (reviewed in Lewis et al., 1998; Widmann et al., 1999; Pearson et al., 2001). The prototypical MAP kinase pathway is the ERK1/2 pathway, which is activated preferentially by mitogenic factors, differentiation stimuli and cytokines.
Prototypical[?pro?t??t?p?kl] is used to indicate that someone or something is a very typical example of a type of person or thing.
The basic principles that govern the activation of this pathway have been established during the 1990s and are relatively well understood. Binding of ligands to their respective cell surface receptors induces the activation of the small GTPase Ras, which recruits the MAP kinase kinase kinase Raf to the membrane for subsequent activation by phosphorylation. Activated Raf isoforms phosphorylate and activate the MAP kinase kinases MEK1/ MEK2, which in turn activate the effector MAP kinases ERK1 and ERK2 by phosphorylation of the Thr and Tyr residues within their activation loop. ERK1/ERK2, which are expressed ubiquitously in mammalian cells, are multifunctional serine/threonine kinases that phosphorylate a vast array of substrates localized in all cellular compartments (Lewis et al., 1998; Pearson et al., 2001; Yoon and Seger, 2006). These include protein kinases, signaling effectors, receptors, cytoskeletal proteins and nuclear transcriptional regulators. This review focuses on the importance of the ERK1/2 MAP kinase pathway in cell proliferation control. We discuss our current understanding of the mechanisms by which activated ERK1/ERK2 regulate growth and cell cycle progression of mammalian somatic cells.
