| Project/Area Number |
09680775
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Fujita Health University |
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Principal Investigator |
TANIGUCHI Hisaaki Inst.Comprehensive Med.Sci., Fujita Health University Assistant Prof., 総合医科学研究所, 助教授 (10257636)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Mamoru Inst.Comprehensive Med.Sci., Fujita Health University Instructor, 総合医科学研究所, 助手 (90288481)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Mass spectrometry / Phosphorylation / Neuron / Neurotransmitter / Protein kinase / Posttranslational modification |
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| Research Abstract |
We have been studying brain-specific phosphoproteins using an LC/MS system, in which a capillary HPLC column is connected on-line to an electrospray mass spectrometer. In this research, our aim is to study posttranslational modifications of brain-specific phosphoproteins such as synapsin I, GAP-43, and MAP1B.These proteins are involved in the neurite extension and synapse formation, and their functions are regulated by the network of protein kinase cascades including MAP kinase and PKC, We could establish an ultra-sensitive assay for in vivo phosphorylation using nanospray ionization method. The results obtained revealed novel phosphorylation sites including Ser (Thr)-Pro motif, suggesting that these proteins are in vivo substrates of so-called proline-directed protein kinase such as MAP kinase and Cdk5, which are highly expressed in the brain. These protein kinases with the SP specificity, therefore, are involved directly in the regulation of neurotransmitter release and synapse formation. We also found that phosphorylation of MAP 1B affected its binding to microtubules. The phosphorylation sites are found near the tubulin-binding site. These results suggest that the proline-directed protein kinases such as MAP kinase play important roles in the regulation of MAP1B function during synaptogenesis.
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