1. ¹Departments of Pharmacology and Molecular Biology, Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Montreal, Quebec, Canada
2. ²Institute of Signaling, Developmental Biology and Cancer, CNRS UMR 6543, Université de Nice-Sofia Antipolis, Centre A. Lacassagne, Nice, France

Correspondence: Dr S Meloche, Departments of Pharmacology and Molecular Biology, Institut de Recherche en Immunologie et Cancérologie Université de Montréal, Montreal, Quebec, Canada H3C 3J7. Email: sylvain.meloche@umontreal.ca; Dr J Pouysségur, Institute of Signaling, Developmental Biology and Cancer, CNRS UMR 6543, Université de Nice-Sofia Antipolis, Centre A Lacassagne, Nice 06189, France. E-mail: jacques.pouyssegur@unice.fr

Abstract

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.