| Project/Area Number |
15370057
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
ITOH Hiroshi Nara Inst.of Sci. & Tech., Cell Biology, Professor, バイオサイエンス研究科, 教授 (10183005)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Norikazu Nara Inst.of Sci. & Tech., Cell Biology, Assi.Professor, バイオサイエンス研究科, 助手 (90212232)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2003: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | G protein / Signal transduction / network / small GTP-binding proteins / guanine nucleotide exchange factor / cell migration / adaptor protein / MAPキナーゼ |
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| Research Abstract |
G protein-coupled receptors(GPCRs) constitute the largest family of seven-transmembrane receptors and are responsible for converting a diverse array of extracellular stimuli into intracellular signaling events with activation of the heterotrimeric GTP-binding regulatory proteins (G proteins). However, the mechanism by which GPCRs lead the multiple cellular responses is not fully understood. We demonstrated that the G protein signaling controls the cell proliferation and cell migration through MAP kinase cascades. In this project, we investigated the molecular mechanism between G protein signaling and MAP kinase cascade in the neural stem cells and transformed cells. In the transformed 293T cells, a novel guanine nucleotide exchange factor(GEF), FRG, was identified to function downstream of G protein. Endothelin-1 stimulated the GEF activity of FRG for Cdc42. We found that FRG is tyrosine-phosphorylated and activated by Src, and involved in the regulation of cell migration by endothelin-1. Furthermore, we demonstrated that an adaptor protein, Nck1, acts as the signal mediator between downstream of GPCR and upstream of Cdc42. Next crucial step is to investigate the relationship between FRG and Nck1. Using the combination of the adenovirus-expression system and the brain slice culture system, we found that GPCR signaling through Gq and JNK negatively regulates the neural progenitor cell migration. Moreover, the crosstalk between G protein signaling and dioxin signaling was revealed.
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