title: Induction of MAP kinase phosphatase 3 through Erk/MAP kinase activation in three oncogenic Ras (H-, K- and N-Ras)-expressing NIH/3T3 mouse embryonic fibroblast cell lines.
abstract: Ras oncoproteins are small molecular weight GTPases known for their involvement in oncogenesis, which operate in a complex signaling network with multiple effectors. Approximately 25% of human tumors possess mutations in a member of this family. The Raf1/MEK/Erk1/2 pathway is one of the most intensively studied signaling mechanisms. Different levels of regulation account for the inactivation of MAP kinases by MAPK phosphatases in a cell type- and stimuli-dependent manner. In the present study, using three inducible Ras-expressing NIH/3T3 cell lines, we demonstrated that MKP3 upregulation requires the activation of the Erk1/2 pathway, which correlates with the shutdown of this pathway. We also demonstrated, by applying pharmacological inhibitors and effector mutants of Ras, that induction of MKP3 at the protein level is positively regulated by the oncogenic Ras/Raf/MEK/Erk1/2 signaling pathway. [BMB Reports 2016; 49(7): 370-375].
authors.affiliation: Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Korea.
authors.forename: JaeHyung
authors.initials: J
authors.lastname: Koo
authors.affiliation: Qiqihar Medical University, Qiqihar City, Heilongjiang Province, 161006, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Korea.
authors.forename: NaNa
authors.initials: N
authors.lastname: Kang
authors.affiliation: Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Korea.
authors.forename: Sun Jin
authors.initials: SJ
authors.lastname: Hur
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju 27478, Korea.
authors.forename: Young Yil
authors.initials: YY
authors.lastname: Bahk
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004318:Doxycycline / Q000633:toxicity; D054642:Dual Specificity Phosphatase 6 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D016296:Mutagenesis; D041681:NIH 3T3 Cells; D009570:Nitriles / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002070:Butadienes; D002867:Chromones; D009025:Morpholines; D009570:Nitriles; C113580:U 0126; D016222:Fibroblast Growth Factor 2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054642:Dual Specificity Phosphatase 6; C517036:Dusp6 protein, mouse; D018631:ras Proteins; D004318:Doxycycline
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