2000 Fiscal Year Annual Research Report

細胞悪性化に関わるCD98シグナル伝達系の解析

Research Project

Project/Area Number	11672157
Research Institution	Kinki University
Principal Investigator	益子高近畿大学, 薬学部, 教授 (30157200)
Co-Investigator(Kenkyū-buntansha)	榎本武美東北大学, 大学院・薬学研究科, 教授 (80107383)
Keywords	CD98 / CD98hc / CD98lc / モノクローナル抗体 / EAAC1 / グルタミン酸受容体 / トロポミオシン
Research Abstract	由来組織を問わず全ての癌細胞で高発現するCD98シグナル伝達系の解明を目的として、CD98hc遺伝子導入細胞の樹立と性状解析を行った。マウス線維芽細胞でCD98hcを過剰発現した結果、飽和密度上昇、軟寒天中コロニー形成及びヌードマウスでの腫瘍形成などの細胞悪性化現象が観察された。このCD98hcによる細胞悪性化にはCD98lcとの結合が必須であること、また、CD98hc細胞外領域の欠失により細胞悪性化が増強されることも明らかとなった。その他にも以下の知見を得ることが出来た。 1)CD98hcとの結合が示唆されているグルタミン酸受容体EAAC1を解析する過程で、欠失型EAAC1を同定、クローン化した。 2)新規CD98lcを認識するモノクローナル抗体を作製し、このCD98lcがCD98hc同様、リンパ球活性化や細胞癌化に伴って発現増強することを見出した。 3)サンドイッチELISAを用いた隣接分子に対するモノクローナル抗体作製法を開発し、CD98隣接分子としてアクチン結合性のトロポミオシンを同定した。

Research Products
(13 results)

All Other

All Publications (13 results)

[Publications] Matsumoto,Y.: "Identification of truncated human glutamate transporter"Tohoku.J.Exp.Med.. 187. 173-182 (1999)
[Publications] Hara,K.: "Malianant transformation of NIH3T3 cells by overexpression of early lymphocyte activation antigen CD98"Biochem.Biophys.Res.Commun.. 262. 720-725 (1999)
[Publications] Matsumoto,Y.: "Identification and Immunological Characterization of a Novel 40-kDa Protein Linked to CD98 Antigen"Cell Struct.Funct.. 24. 217-226 (1999)
[Publications] Shiratori,M: "Detection by epitope-defined monoclonal antibodies of Werner DNA helicases in the nucleoplasm and their upregulation by cell transformation and immortalization"J Cell Biol.. 144. 1-9 (1999)
[Publications] Shishido,T.: "Colocalization of GP125/CD98 with tropornyosin isoforms at the cell-cell adhesion boundary"J.Biochem.. 127. 253-261 (2000)
[Publications] Sishido,T.: "Transformation of Balb3T3 cells caused by over-expression of rat CD98 heavy chain (hc) recquires its association with light chain : Missense mutation in a cysteine resldue of CD98hc-eliminates its transforming activity-"Int.J.Cancer. 87. 311-316 (2000)
[Publications] Onoda,F.: "Elevation of the slster chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom's syndrome gene"Mutat.Res.. 459. 203-209 (2000)
[Publications] Miyajima,A.: "Sgs1 helicase activity is required for mitotic but apparently not for meiotic functions"Mol.Cell.Biol.. 20. 6399-6409 (2000)
[Publications] Onoda,F,: "Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae"Mol.Gen.Genet.. 264. 702-708 (2001)
[Publications] Hara,K.: "Enhanced tumorigenicity caused by truncation of the extracellular domain of GP125/CD98 heavy chain"Oncogene. 19. 6209-6215 (2000)
[Publications] Wang,W.: "Possible association of BLM in decreasing DNA double strand breaks during DNA replication"EMBO J.. 19. 3428-3435 (2000)
[Publications] Kawabe,Y,: "Covalent modification of the Werner's syndrome gene product with the ubiquitin-related protein, SUMO-1"J.Biol.Chem.. 275. 20963-20966 (2000)
[Publications] Kawabe,T,: "Differential regulation of human RecQ family helicases in cell transformation and cell cycle"Oncogene . 19. 4764-4772 (2000)

2000 Fiscal Year Annual Research Report

細胞悪性化に関わるCD98シグナル伝達系の解析

Principal Investigator

益子 高 近畿大学, 薬学部, 教授 (30157200)

Research Products

[Publications] Matsumoto,Y.: "Identification of truncated human glutamate transporter"Tohoku.J.Exp.Med.. 187. 173-182 (1999)

[Publications] Hara,K.: "Malianant transformation of NIH3T3 cells by overexpression of early lymphocyte activation antigen CD98"Biochem.Biophys.Res.Commun.. 262. 720-725 (1999)

[Publications] Matsumoto,Y.: "Identification and Immunological Characterization of a Novel 40-kDa Protein Linked to CD98 Antigen"Cell Struct.Funct.. 24. 217-226 (1999)

[Publications] Shiratori,M: "Detection by epitope-defined monoclonal antibodies of Werner DNA helicases in the nucleoplasm and their upregulation by cell transformation and immortalization"J Cell Biol.. 144. 1-9 (1999)

[Publications] Shishido,T.: "Colocalization of GP125/CD98 with tropornyosin isoforms at the cell-cell adhesion boundary"J.Biochem.. 127. 253-261 (2000)

[Publications] Sishido,T.: "Transformation of Balb3T3 cells caused by over-expression of rat CD98 heavy chain (hc) recquires its association with light chain : Missense mutation in a cysteine resldue of CD98hc-eliminates its transforming activity-"Int.J.Cancer. 87. 311-316 (2000)

[Publications] Onoda,F.: "Elevation of the slster chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom's syndrome gene"Mutat.Res.. 459. 203-209 (2000)

[Publications] Miyajima,A.: "Sgs1 helicase activity is required for mitotic but apparently not for meiotic functions"Mol.Cell.Biol.. 20. 6399-6409 (2000)

[Publications] Onoda,F,: "Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae"Mol.Gen.Genet.. 264. 702-708 (2001)

[Publications] Hara,K.: "Enhanced tumorigenicity caused by truncation of the extracellular domain of GP125/CD98 heavy chain"Oncogene. 19. 6209-6215 (2000)

[Publications] Wang,W.: "Possible association of BLM in decreasing DNA double strand breaks during DNA replication"EMBO J.. 19. 3428-3435 (2000)

[Publications] Kawabe,Y,: "Covalent modification of the Werner's syndrome gene product with the ubiquitin-related protein, SUMO-1"J.Biol.Chem.. 275. 20963-20966 (2000)

[Publications] Kawabe,T,: "Differential regulation of human RecQ family helicases in cell transformation and cell cycle"Oncogene . 19. 4764-4772 (2000)

益子高近畿大学, 薬学部, 教授 (30157200)