博士 / 國防醫學院 / 生命科學研究所 / 91 / Tyrosine kinase phosphorylation plays an important role in the induction of long-term potentiation (LTP). Tyrosine kinases can be divided into two categories. One is the membrane-spanning receptor tyrosine kinase and the other is the non-receptor tyrosine kinase. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase which shows decreased phosphorylation in fyn-mutant mice and Fyn plays a critical role in LTP induction. By examining the role of FAK involved in LTP induction in dentate gyrus neurons in vivo upon dorsomedial perforant path stimulation , we found that both FAK and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) phosphory- lation were significantly increased 5 min and 10 min after LTP induction, while cAMP-responsive element binding protein (CREB) phosphory- lation was increased 40 min later. Transfection of the FAK mutant construct HA-FAK(Y397F) impaired LTP, whereas transfection of the constitutively activated form HA-FAK(1-100) reduced the threshold for LTP induction. Transfection of HA-FAK(1-100) by itself did not induce long-lasting potentiation. Further, transfection of the HA-FAK(Y397F) construct decreased FAK, MAPK/ERK and CREB phosphorylation, and inhibition of MAPK/ERK decreased CREB phosphorylation. Moreover, blockade of NMDA receptor (NMDAR) did not decrease FAK, MAPK/ERK and CREB phosphorylation even though LTP induction was blunted by NMDAR antagonist. These biochemical changes were not associated with low frequency stimulation. Immunoprecipitation results revealed that tyrosine phosphorylation of NR2A and NR2B as well as the association of phosphorylated FAK with NR2A and NR2B were increased upon LTP induction. These results together suggest that FAK is required, but not sufficient, for the induction of LTP in a NMDAR-independent manner and that MAPK/ERK and CREB are the downstream events of FAK activation. Further, FAK may interact with NR2A and NR2B to modulate LTP induction.
| Identifer | oai:union.ndltd.org:TW/091NDMC0105019 |
| Date | January 2003 |
| Creators | Ying Chen Yang, 楊瀅臻 |
| Contributors | Eminy HY Lee, 李小媛 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 117 |
Page generated in 0.1067 seconds