The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition ERK1/2 MAP kinases in cell cycle control

Departments of Pharmacology and Molecular Biology, Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Montreal, Quebec, Canada.
Oncogene (Impact Factor: 8.46). 06/2007; 26(22):3227-39. DOI: 10.1038/sj.onc.1210414
Source: PubMed


The Ras-dependent extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway plays a central role in cell proliferation control. In normal cells, sustained activation of ERK1/ERK2 is necessary for G1- to S-phase progression and is associated with induction of positive regulators of the cell cycle and inactivation of antiproliferative genes. In cells expressing activated Ras or Raf mutants, hyperactivation of the ERK1/2 pathway elicits cell cycle arrest by inducing the accumulation of cyclin-dependent kinase inhibitors. In this review, we discuss the mechanisms by which activated ERK1/ERK2 regulate growth and cell cycle progression of mammalian somatic cells. We also highlight the findings obtained from gene disruption studies.

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Available from: Jacques Pouysségur, Mar 26, 2015
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    • "In diverse cell types, including fibroblasts, ERK1/2 activation in response to mitogenic stimuli promotes cell proliferation [53]. In particular, a number of evidence indicates that sustained activation of ERK1/2 signaling is required for G1-to S-phase progression and is accompanied by induction of positive regulators of cell cycle [54]. Furthermore, LPA has long been known to stimulate fibroblasts proliferation through PTX-sensitive G proteins [35] [36]. "
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    • "These findings indicate that the diabetes-induced RPE cell proliferation may be mediated by ERK signaling. The ERK1 (p44) and ERK2 (p22) are known to be activated by mitogenic factors and that this biochemical change stimulates cell division (Meloche and Pouyssegur, 2007). As the cell proliferation was investigated at the early stage, that is, at the end of second week, the low or moderate level of oxidative stress might have stimulated the expression of the ERKs to mediate the cell proliferation. "
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    • "There is now much evidence to suggest that the proliferation of many cell types is under the control of redoxregulated signalling pathways (reviewed in [5]). In particular the ERK1/2 signalling cascade, activated by intracellular-generated reactive oxygen species (ROS) acts to promote proliferation in various cell types [6] [7] [8]. An important molecular mechanism underlying this ERK1/2 activation is thought to be the ROS-dependent inactivation of protein tyrosine phosphatases (PTPs) (reviewed in [9]). "
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