title: MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm.
abstract: MAPK phosphatase-7 (MKP-7) was identified as a JNK-specific phosphatase. However, despite its high specificity for JNK, MKP-7 interacts also with ERK. We previously showed that as a physiological consequence of their interaction, activated ERK phosphorylates MKP-7 at Ser-446, and stabilizing MKP-7. In the present study, we analyzed MKP-7 function in activation of ERK. A time-course experiment showed that both MKP-7 and its phosphatase-dead mutant prolonged mitogen-induced ERK phosphorylation, suggesting that MKP-7 functions as a scaffold for ERK. An important immunohistological finding was that nuclear translocation of phospho-ERK following PMA stimulation was blocked by co-expressed MKP-7 and, moreover, that phospho-ERK co-localized with MKP-7 in the cytoplasm. Reporter gene analysis indicated that MKP-7 blocks ERK-mediated transcription. Overall, our data indicate that MKP-7 down-regulates ERK-dependent gene expression by blocking nuclear accumulation of phospho-ERK.
authors.affiliation: Miyagi Cancer Center Research Institute, Natori, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Masuda
authors.forename: Chiaki
authors.initials: C
authors.lastname: Katagiri
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nomura
authors.forename: Masami
authors.initials: M
authors.lastname: Sato
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kakumoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Akagi
authors.forename: Kunimi
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tanuma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shima
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000201:enzymology; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000201:enzymology*; D015536:Down-Regulation; D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D004815:Epidermal Growth Factor; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C439065:DUSP16 protein, human; D054637:Dual-Specificity Phosphatases