2003 Fiscal Year Annual Research Report

マスト細胞の不活性化に関与する分子の同定

Research Project

Project/Area Number	13557040
Research Institution	The University of Tokyo
Principal Investigator	北村俊雄東京大学, 医科学研究所, 教授 (20282527)
Keywords	マスト細胞 / シグナルシークエンス / PIR / ITIMモチーフ / アレルギー
Research Abstract	マウス骨髄細胞由来培養マスト細胞からSST-REXのライブラリーを作成し、シグナルシークエンストラップを行い、計2400のSSTクローン得た。機能未知のcDNAは20%存在したが、そのうち抑制型NKレセプターに相同性を有する免疫グロビンスーパーファミリーに属するI型膜蛋白質に注目した。この分子は細胞外ドメインに1つの免疫グロビン様モチーフを、細胞内には3ないし4つのITIM(免疫抑制)モチーフを有する分子で、マスト細胞以外にB細胞、骨髄系細胞に発現しており、LMIR-1 (leukocyte-associated mono-Ig receptor-1)と命名した。またデータベースを調べることによってLMIR-1に相同性を有するLMIR-2、3、4、5、6を同定し、全長cDNAをクローニングした。これらの分子のうち、LMIR-1とLMIR-3は細胞内ドメインにITIMモチーフを有する抑制型レセプターであるのに対して、LMIR-2、4、5、6は細胞内部位が短く、膜貫通部位に親水性アミノ酸を有し、DAP10、DAP12、FcRγというITA(免疫活性)モチーフを有する活性化レセプターと会合するレセプターであることが判明した。現在までに、各LMIR分子に対する単クローン抗体を作成し、LMIR-1は脱リン酸化酵素SHP1、SHP2およびSHIPのリン酸化を介して抑制のシグナルを、またLMIR-2はDAP10、DAP12、FcRγと会合することにより活性化のシグナルを細胞内に送ることを明らかにした。今後レセプターのリガンドの同定やノックアウトマウスの作成を行うことによって、レセプターの生理的役割を明らかにしていきたい。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Yujiri, T.: "MEK kinase 1 interacts with focal adhesion kinase and regulates insulin receptor Substrate-1 expression."The Journal of Biological Chemistry. 278. 3846-3851 (2003)
[Publications] Ozawa, T.: "A genetic approach to identifying mitochondrial proteins."Nature Biotechnology. 21. 287-293 (2003)
[Publications] Minoshima, Y.: "Phosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis."Developmental Cell. 4. 549-560 (2003)
[Publications] Nosaka, T.: "Mammalian twisted gastulation is essential for skeleto-lymphogenesis."Molecular and Cellular Biology. 23. 2969-2980 (2003)
[Publications] Kitamura, T.: "Retrovirus-mediated gene transfer and expression cloning, powerful tools in functional genomics."Experimental Hematology. 31. 1007-1014 (2003)
[Publications] Bao, Y-C.: "Identification of a human cDNA sequence which encodes a novel membrane-associated protein containing a zinc metalloprotease motif."DNA Research. 10. 123-128 (2003)
[Publications] Murata, K.: "A novel tyrosine kinase inhibitor GTP14564 specifically inhibits constitutively active fins-like tyrosine kinase 3 through inactivation of STAT5."The Journal of Biological Chemistry. 278. 32892-32898 (2003)
[Publications] Ueno, H.: "A stromal cell-derived membrane protein that supports hematopoietic stem cells."Nature Immunology. 4. 457-463 (2003)
[Publications] Hisaoka, T.: "Expression of a member of tumor necrosis factor receptor superfamily, TROY, in the developing and the adult mouse brain."Brain Research. 143. 105-109 (2003)
[Publications] Takizawa, M.: "Requirement of gp130 signaling for the AGM hematopoiesis."Experimental Hematology. 31. 283-289 (2003)
[Publications] Tahara, H.: "Reconstitution of CD8+T cells by retroviral transfer of the T-cell receptor ab chain genes isolated from a clonally expanded P815 infiltrating lymphocytes."The Journal of Immunology. 171. 2154-2160 (2003)
[Publications] Kumagai, H.: "Identification and characterization of a new pair of immunoglobulin-like receptors LMIR1 and 2 derived from murine bone marrow-derived mast cells."Biochemical and Biophysical Research Communications. 307. 719-729 (2003)

2003 Fiscal Year Annual Research Report

マスト細胞の不活性化に関与する分子の同定

Principal Investigator

北村 俊雄 東京大学, 医科学研究所, 教授 (20282527)

Research Products

[Publications] Yujiri, T.: "MEK kinase 1 interacts with focal adhesion kinase and regulates insulin receptor Substrate-1 expression."The Journal of Biological Chemistry. 278. 3846-3851 (2003)

[Publications] Ozawa, T.: "A genetic approach to identifying mitochondrial proteins."Nature Biotechnology. 21. 287-293 (2003)

[Publications] Minoshima, Y.: "Phosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis."Developmental Cell. 4. 549-560 (2003)

[Publications] Nosaka, T.: "Mammalian twisted gastulation is essential for skeleto-lymphogenesis."Molecular and Cellular Biology. 23. 2969-2980 (2003)

[Publications] Kitamura, T.: "Retrovirus-mediated gene transfer and expression cloning, powerful tools in functional genomics."Experimental Hematology. 31. 1007-1014 (2003)

[Publications] Bao, Y-C.: "Identification of a human cDNA sequence which encodes a novel membrane-associated protein containing a zinc metalloprotease motif."DNA Research. 10. 123-128 (2003)

[Publications] Murata, K.: "A novel tyrosine kinase inhibitor GTP14564 specifically inhibits constitutively active fins-like tyrosine kinase 3 through inactivation of STAT5."The Journal of Biological Chemistry. 278. 32892-32898 (2003)

[Publications] Ueno, H.: "A stromal cell-derived membrane protein that supports hematopoietic stem cells."Nature Immunology. 4. 457-463 (2003)

[Publications] Hisaoka, T.: "Expression of a member of tumor necrosis factor receptor superfamily, TROY, in the developing and the adult mouse brain."Brain Research. 143. 105-109 (2003)

[Publications] Takizawa, M.: "Requirement of gp130 signaling for the AGM hematopoiesis."Experimental Hematology. 31. 283-289 (2003)

[Publications] Tahara, H.: "Reconstitution of CD8+T cells by retroviral transfer of the T-cell receptor ab chain genes isolated from a clonally expanded P815 infiltrating lymphocytes."The Journal of Immunology. 171. 2154-2160 (2003)

[Publications] Kumagai, H.: "Identification and characterization of a new pair of immunoglobulin-like receptors LMIR1 and 2 derived from murine bone marrow-derived mast cells."Biochemical and Biophysical Research Communications. 307. 719-729 (2003)

北村俊雄東京大学, 医科学研究所, 教授 (20282527)