| Project/Area Number |
06454645
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Structural biochemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
MURAMATSU Takashi Nagoya University, School of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (00030891)
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| Co-Investigator(Kenkyū-buntansha) |
MURAMATSU Hisako Nagoya University, School of Medicine, Department of Biochemistry, Assistanat Pr, 医学部, 助手 (50182134)
KADOMATSU Kenji Nagoya University, School of Medicine, Department of Biochemistry, Assistant Pro, 医学部, 講師 (80204519)
KANEDA Norio Nagoya University, School of Medicine, Department of Biochemistry, Associate Pro, 医学部, 助教授 (00144139)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1995: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1994: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | midkine / heparin / growth factor / tissue repair / receptor / heparan sulfate / neurite outgrowth / cancer / ヘパリン硫酸 / レチノイン酸 / プラズミノーゲン活性化酵素 |
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| Research Abstract |
We studied on structure and function of midkine (MK). Chemically synthesized C-terminal half molecule of MK has neurite outgrowth promoting activity and heparin binding activity. A mutant MK whose putative heparin binding sites were altered by in vitro mutagenesis lost neurite promoting activity, indicating that heparing binding activity correlates with neurite promoting activity. Structural requirements for binding to MK was analyzed by chemically modified heparing and heparin-derived oligosaccharides. All of sulfate groups (2-0,6-0,2-N) were required for inhibition of neurite promoting activity. The size of heparin oligosaccharide necessary for the inhibition was about 20-mer. On the other hand, a putative MK receptor was disclosed by analysis of membrane proteins binding to MK column. A histochemical method to localize the MK receptor of protein nature was also established. We also obtained results indicating the correlation of MK expression and cancer, brain and heart infarction and rheumatoid arthritis. A sensitive method to determine MK levels was also devised, enabling MK assay in serum samples.
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