Prolonged Nuclear Retention of Activated Extracellular Signal-regulated Kinase 1/2 Is Required for Hepatocyte Growth Factor-induced Cell Motility

作者: Susumu Tanimura , Kayo Nomura , Kei-ichi Ozaki , Masafumi Tsujimoto , Takahito Kondo

DOI: 10.1074/JBC.M202866200

关键词: Signal transductionBiologyHepatocyte growth factorExtracellularCell biologyMolecular biologyStimulationMAPK/ERK pathwayMotilityKinaseCytoplasm

摘要: We examined the signaling pathway by which hepatocyte growth factor (HGF) induces cell motility, with special focus on role of extracellular signal-regulated kinase (ERK) in nucleus. used Madin-Darby canine kidney cells overexpressing ERK2 because their prominent motility response to HGF. HGF stimulation not only a rapid, marked, and sustained activation rapid nuclear accumulation ERK1/2, but also prolonged retention activated ERK1/2. Interruption ERK1/2 PD98059 treatment 30 min after abolishes HGF-induced motility. Enforced cytoplasmic expression an inactive form MKP-3 phosphatase inhibits response. Although epidermal it does induce fails In nucleus, continuously phosphorylate Elk-1, leading c-fos, results several genes such as matrix metalloproteinase(mmp)-9; MMP-9 activity is required for induction Our indicate that nucleus

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