title: MKP-1: a critical phosphatase in the biology of macrophages controlling the switch between proliferation and activation.
abstract: Macrophages play a central role in the immune response. These cells either proliferate in response to, for example, growth factors or become activated in response to, for example, LPS and develop functional activities. Experiments carried out in mice showed that macrophage proliferation requires a short period of ERK phosphorylation, while an extended period is required for macrophage activation. The length of phosphorylation is controlled by the MAPK phosphatase-1 (MKP-1), a nuclear-localized dual-specificity phosphatase that dephosphorylates the MAPKs ERK, p38, and c-Jun NH(2) -terminal kinase (JNK). MKP-1 is induced in macrophages by growth factors, as well as by activators such as LPS, but with different kinetics; to achieve the different functional outcomes (proliferation versus activation), the inhibition of MKP-1 by cytokines such as IFN-γ blocks macrophage proliferation and induces activation. The data presented in this review show that this phosphatase is the switch between macrophage proliferation and activation.
authors.affiliation: Macrophage Biology Group, Institute for Research in Biomedicine Barcelona, Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Comalada
authors.forename: Jorge
authors.initials: J
authors.lastname: Lloberas
authors.forename: Antonio
authors.initials: A
authors.lastname: Celada
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D054638:Dual Specificity Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation
chemical_list: D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D054638:Dual Specificity Phosphatase 1