title: Reciprocal actions of NCAM and tPA via a Ras-dependent MAPK activation in rat hippocampal neurons.
abstract: In an attempt to identify the functions of neural cell adhesion molecule (NCAM) and tissue plasminogen activator (tPA) in hippocampal synaptic plasticity, we investigated the relationship between the two molecules by focusing on mitogen-activated protein kinase (MAPK), an essential enzyme in this process. NCAM clustering in cultured hippocampal neurons transiently induced MAPK within 10min. Moreover, soluble NCAM also induced a Ras-dependent MAPK activation. Conversely, MAPK activation led to an increase in the expressions of all three isoforms of NCAM. Treatment of neurons with tPA and plasminogen induced a Ras-dependent MAPK activation and tPA-plasmin degradation of NCAM was mediated in a MAPK-dependent manner. Soluble NCAM transiently inhibited tPA mRNA expression levels in a MAPK-dependent manner, while stimulation of MAPK alone induced tPA reduction in cells. These results collectively indicate that NCAM and tPA reciprocally act as important regulators in the modulation of synaptic plasticity via a Ras-MAPK-involved signaling pathway. In turn, MAPK activation may cause tPA degradation or a decrease in expression to promote synaptic plasticity.
authors.affiliation: Department of Biochemistry, Hanyang University College of Medicine, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, South Korea.
authors.forename: Hyeon
authors.initials: H
authors.lastname: Son
authors.forename: Jin
authors.initials: J
authors.lastname: Seuk Kim
authors.forename: Jung
authors.initials: J
authors.lastname: Mogg Kim
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D019006:Neural Cell Adhesion Molecules / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D051381:Rats; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
chemical_list: D019006:Neural Cell Adhesion Molecules; D010958:Plasminogen; D020928:Mitogen-Activated Protein Kinases; D010959:Tissue Plasminogen Activator; D016283:Proto-Oncogene Proteins p21(ras)