title: ERK implication in cell cycle regulation.
abstract: The Ras/Raf/MEK/ERK signaling cascade that integrates an extreme variety of extracellular stimuli into key biological responses controlling cell proliferation, differentiation or death is one of the most studied intracellular pathways. Here we present some evidences that have been accumulated over the last 15 years proving the requirement of ERK in the control of cell proliferation. In this review we focus (i) on the spatio-temporal control of ERK signaling, (ii) on the key cellular components linking extracellular signals to the induction and activation of cell cycle events controlling G1 to S-phase transition and (iii) on the role of ERK in the growth factor-independent G2/M phase of the cell cycle. As ERK pathway is often co-activated with the PI3 kinase signaling, we highlight some of the key points of convergence leading to a full activation of mTOR via ERK and AKT synergies. Finally, ERK and AKT targets being constitutively activated in so many human cancers, we briefly touched the cure issue of using more specific drugs in rationally selected cancer patients.
authors.affiliation: Institute of Signaling Developmental Biology and Cancer, CNRS UMR 6543, Universite de Nice-Sofia Antipolis, Centre A. Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Chambard
authors.forename: Renaud
authors.initials: R
authors.lastname: Lefloch
authors.forename: Jacques
authors.initials: J
authors.lastname: Pouysségur
authors.forename: Philippe
authors.initials: P
authors.lastname: Lenormand
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases