title: A new ERK2 binding protein, Naf1, attenuates the EGF/ERK2 nuclear signaling.
abstract: Extracellular signal regulated kinase1/2 (ERK1/2), an important factor in signal transduction, controls cell growth, differentiation, and death. To elucidate the details of the mechanism of ERK1/2 signaling in human cells, we isolated Nef-associated factor 1 alpha (Naf1 alpha) by a yeast two-hybrid system, which bound to human ERK2. The binding was confirmed by a pull-down assay in vitro and immunoprecipitation in vivo. Upon EGF treatment, Naf1 alpha was phosphorylated by the EGF/MEK/ERK2 signal transduction pathway. To identify the role of Naf1 alpha in the ERK2 signaling, Naf1 alpha-expressing Saos-2 cells were analyzed for ERK2 nuclear translocation and activation of its downstream target. Overexpression of Naf1 alpha suppressed ERK2 entering into the nucleus and inhibited the ERK2-dependent Elk1-driven luciferase transcription, suggesting Naf1 alpha to be an attenuator of activated ERK2 signaling.
authors.affiliation: Department of Molecular Cellular Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo 113, Japan.
authors.forename: Shengliang
authors.initials: S
authors.lastname: Zhang
authors.forename: Masaya
authors.initials: M
authors.lastname: Fukushi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Chongfeng
authors.initials: C
authors.lastname: Gao
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Fukuyo
authors.forename: Takuma
authors.initials: T
authors.lastname: Nakajima
authors.forename: Teruo
authors.initials: T
authors.lastname: Amagasa
authors.forename: Shoji
authors.initials: S
authors.lastname: Enomoto
authors.forename: Katsuro
authors.initials: K
authors.lastname: Koike
authors.forename: Osamu
authors.initials: O
authors.lastname: Miura
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tsuchida
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism* / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; C117046:TNIP1 protein, human; D004815:Epidermal Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases