title: Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation.
abstract: The MAP kinase ERK2 is widely involved in eukaryotic signal transduction. Upon activation it translocates to the nucleus of the stimulated cell, where it phosphorylates nuclear targets. We find that nuclear accumulation of microinjected ERK2 depends on its phosphorylation state rather than on its activity or on upstream components of its signaling pathway. Phosphorylated ERK2 forms dimers with phosphorylated and unphosphorylated ERK2 partners. Disruption of dimerization by mutagenesis of ERK2 reduces its ability to accumulate in the nucleus, suggesting that dimerization is essential for its normal ligand-dependent relocalization. The crystal structure of phosphorylated ERK2 reveals the basis for dimerization. Other MAP kinase family members also form dimers. The generality of this behavior suggests that dimerization is part of the mechanism of action of the MAP kinase family.
authors.affiliation: Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas 75235-9041, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Khokhlatchev
authors.forename: B
authors.initials: B
authors.lastname: Canagarajah
authors.forename: J
authors.initials: J
authors.lastname: Wilsbacher
authors.forename: M
authors.initials: M
authors.lastname: Robinson
authors.forename: M
authors.initials: M
authors.lastname: Atkinson
authors.forename: E
authors.initials: E
authors.lastname: Goldsmith
authors.forename: M H
authors.initials: MH
authors.lastname: Cobb
mesh_terms: D000818:Animals; D001692:Biological Transport; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D019281:Dimerization; D004789:Enzyme Activation; D005347:Fibroblasts; D019950:Mitogen-Activated Protein Kinase 1; D008958:Models, Molecular; D009154:Mutation; D010766:Phosphorylation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1