| Project/Area Number |
06454592
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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 |
Biological pharmacy
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| Research Institution | HOKKAIDO UNIEVERSITY |
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Principal Investigator |
UENO Naoto Hokkaido Univ., Fac.of Pharm.Sci., Professor, 薬学部, 教授 (40221105)
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| Co-Investigator(Kenkyū-buntansha) |
TADA Masazumi Hokkaido Univ., Fac.of Pharm.Sci., Instructor, 薬学部, 助手 (60216976)
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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 |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1995: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | BMP / bone formation / receptor / Ser / Thr kinase / スレオニンキナーゼ / 骨形成因子 / TGF-βスーパーファミリー / 自己リン酸化 |
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| Research Abstract |
We have isolated several novel receptor Ser/Thr kinase cDNAs from a mouse MC3T3-E1 cells cDNA using oligonucleotide primers designed in the conserved sequence among TGF-beta family receoptors such as activin and TGF-beta type II receptors. One of them designated as mTFR11turned out to be a type I class of receptor that binds both BMP-2 and BMP-4. We constructed a mutantreceptor cDNA that predicts a truncated receptor lacking entire Ser/Thr kinase and confirmed that the dominant negative receptor inhibited both BMP-2 and BMP-4 in cultured osteoblastic cells and in early embryos. Moreover, we generated constitutively active form ofthe BMP receptor by a point mutation Gln to Asp in GS domain, which is believed to be essential for BMP signaling. We further confirmed that the mutant receptor transmits BMP-like signals independent of BMP ligands.
Our effort is now focused on the identification of downstream factor that mediates BMP signaling. Therefore, we have screened a human cDNA library by yeast two-hybrid method using a cytoplasmic region of the BMP receptor as a bait. Successfully, we have isolated three cDNAs that encodes proteins that binds BMP receptor and function of the proteins in the signal transduction is currently investigated.
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