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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yamaguchi, T. Hayashi, T. Yamamoto, T. Nawa, H. Narisawa-saito, M. Silva, A. J. |
| Description | Author Affiliation: Narisawa-Saito M ( Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.); |
| Abstract | Src-family protein tyrosine kinases (PTKs) transduce signals to regulate neuronal development and synaptic plasticity. However, the nature of their activators and molecular mechanisms underlying these neural processes are unknown. Here, we show that brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor enhance expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor 1 and 2/3 proteins in rodent neocortical neurons via the Src-family PTK(s). The increase in AMPA receptor levels was blocked in cultured neocortical neurons by addition of a Src-family-selective PTK inhibitor. Accordingly, neocortical cultures from Fyn-knockout mice failed to respond to BDNF whereas those from wild-type mice responded. Moreover, the neocortex of young Fyn mutants exhibited a significant in vivo reduction in these AMPA receptor proteins but not in their mRNA levels. In vitro kinase assay revealed that BDNF can indeed activate the Fyn kinase: It enhanced tyrosine phosphorylation of Fyn as well as that of enolase supplemented exogenously. All of these results suggest that the Src-family kinase Fyn, activated by the growth factors, plays a crucial role in modulating AMPA receptor expression during brain development. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 96 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1999-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Gene Expression Regulation Growth Substances Pharmacology Neocortex Physiology Neurons Proto-Oncogene Proteins Metabolism Receptors, AMPA Genetics Signal Transduction Animals Brain-Derived Neurotrophic Factor Cells, Cultured Crosses, Genetic Epidermal Growth Factor Fibroblast Growth Factor 2 Drug Effects Mice Mice, Inbred C57BL Mice, Knockout Cytology Platelet-Derived Growth Factor Protein-Tyrosine Kinases Deficiency Proto-Oncogene Proteins C-fyn RNA, Messenger Rats, Sprague-Dawley Receptors, Glutamate Receptors, N-Methyl-D-Aspartate Transcription, Genetic Src-Family Kinases Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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