| Project/Area Number |
01044115
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Kumamoto University |
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Principal Investigator |
TAKATSU Kiyoshi Professor Dept. of Biology, Inst. for Med. Immunol., Kumamoto U. Med. Sch., 医学部, 教授 (10107055)
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| Co-Investigator(Kenkyū-buntansha) |
ポール キンケード オクラホマ医学研究センター, 部長
ケンドール スミス ダートマス大学, 医学部, 教授
フリッツ メルシャーズ バーゼル免疫研究所, 所長
等 泰道 熊本大学, 医学部, 助手 (10222241)
TOMINAGA Akira Associate Professor Dept. of Biology, Inst. for Med. Immunol., Kumamoto U. Med., 医学部, 助教授 (50172193)
MELCHERS Fritz Director Basel Inst. Immunol.
SMITH Kendall Professor Dept. of Medicine, Dartmouth Med. Sch.
YASUMICHI Hitoshi Dept. of Biology, Inst. for Med. Immunol., Kumamoto U. Med. Sch.
KINCADE Paul Professor, chairman Dept. Immunobiol., Oklahoma Med. Res. Fndn.
キンケード ポール オクラホマ医学研究センター, 部長
スミス ケンドール ダートマス大学, 医学部, 教授
メルシャーズ フリッツ バーゼル免疫研究所, 所長
山口 直人 熊本大学, 医学部, 助手 (00166620)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 1991: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1990: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1989: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Interleukin-5 (IL-5) / IL-3 / GM-CSF / Cytokine / IL-5 receptor / Cytokine receptor family / cDNA cloning / B cell growth and differentiation / Eosinophil growth and differentiation / クロスハイブリダイゼ-ション / TFー1 / ILーS受容体 / ILーS受容体cDNA / サイトカインレセプタ- / B前駆細胞株 / ストロ-マ細胞 / 骨髄長期培養 |
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| Research Abstract |
We have characterized human IL-5 receptor (hIL-5R) by cloning cDNA with cross-species hybridization using murine IL-5R alpha chain cDNA as a probe. One cDNA clone encodes a glycoprotein of 420 amino acids (Mr 47, 670) with an N-terminal hydrophobic region (20 amino acids), a glycosylated extracellular domain (324 amino acids), a transmembrane domain (21 amino acids) and a cytoplasmic domain (55 amino acids).
COS7 cells transfected with the cDNA expressed a 6OkD protein and bound IL-5 with a single class of affinity (Kd : 250-590 pM). The Kd values were similar with that observed in normal human eosinophils. The hIL-5R alpha chain characterized in this paper is an essential molecule for signal transduction, because expression of this molecule in murine IL-3 dependent cell line FDC-P1 allow these cells to proliferate in response to IL-5.
In contrast to murine 60 kD alpha chain that binds IL-5 with low affinity (Kd : -IO nM), human alpha chain can bind IL-5 With much higher affinity by itself. In murine system, coexpression of beta chain (AIC2B, IL-3R homologue) with alpha chain increased the affinity at least 100-fold to that of alpha chain alone. Although hIL-5R alpha chain probably makes heterodyne with human GM-CSF receptor beta chain shared with IL-3 receptor, the contribution of hIL-5R beta chain to the increase of the affinity of alpha chain seems to be marginal. This may provide us an easier way to regulate eosinophil growth in human by designing an antagonist to hIL-5R alpha chain.
We have also characterized several other cDNA clones for hIL-5R alpha chain with diversified 3' end. One of which does not have the transmembrane and cytoplasmic domains and probably codes for a soluble form of IL-5R alpha chain. These diversified 3' end may be involved in the regulation of the growth and differentiation of human eosinophils.
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