1989 年度実績報告書

発癌と細胞増殖制御におけるリン酸化チロシンタン白の役割

研究課題

研究課題/領域番号	01010062
研究機関	東海大学
研究代表者	渡辺泰東海大学, 医学部, 教授 (60055746)
研究分担者	上原至雅国立予防衛生研究所, 室長 (50160213) 西沢誠東京大学, 医科研, 助手 (30192248) 井原征治東海大学, 医学部, 教授 (50096202) 小野魁日本大学, 医学部, 教授 (30004675) 瀬川薫慶応大学, 医学部, 講師 (30114523)
キーワード	リン酸化チロシン / チロシンキナーゼ / 細胞増殖因子 / インスリン受容体 / インターロイキン2受容体 / erbBー2 / 乳癌
研究概要	1.増殖因子受容体の構造を変えてチロシンキナーゼ(TK)活性の役割を探る。 TK活性を持つ増殖因子受容体にはGlyーXーGlyーXーXーGlyの構造が共通にある。三番目のGlyがValに変異したインスリン受容体遺伝子をCHO細胞で発現させたところ、TK活性はなく、また各種のインスリン作用を伝達し得なかった。この構造が重要であることを示す(春日)。新しい増殖因子受容体と考えられるerbBー2蛋白の構造を人為的に変える方法で、Cー末端約200アミノ酸配列がTK活性を抑制すること、また、TKドメインのチロシン残基がTK活性を促進的に調節していることがわかった。この蛋白は乳癌などに高頻度に発現されており、これを指標とした癌の診断が有望であることがわかった(秋山)。 2.リンパ球増殖の初期信号伝達にもTK活性が関わる。インターロイキン2(ILー2)によるリンパ球の増殖刺激は高親和性のILー2受容体(alfa鎖とbeta鎖)を介して伝達される。この刺激によりbeta鎖のチロシン残基が燐酸化されることを発見した。リンパ球に特異なTK活性がありこれがbeta鎖と会合していることが推定された(中村)。リンパ球の増殖に関わる可能性があるTK活性の部分精製もなされた(小野)。 3.その他の班員の成果は字数制限のため省略。

研究成果

(23件)

すべてその他

すべて文献書誌 (23件)

[文献書誌] Makoto Nishizawa: "v-maf,a aviral oncogene that encodes a "leucine zipper"motif." Proc.Natl.Acad.Sci.USA. 86. 7711-7715 (1989)
[文献書誌] Sadaaki Kawai: "A Variant Schmidt-Ruppin Strain of Rous Sarcoma Virus with Increased Affinity for Mammalian Cells." Jpn.J.Cancer Res.80. 1179-1185 (1989)
[文献書誌] Kentaro Semba: "Transformation of Chicken Embryo Fibroblast Cells.by Avian Retoviruses containing the human Fyn gene and Its Mutated Genes." Mol.Cell.Biol.
[文献書誌] Takayama-Hasumi,S.: "Autoantibodies to the insulin(B-10)can stimulate tyrosine phosphorylation of the β-subunit of the insulin receptor and a 185,000 MW protein in rat hepatoma cells." J.Clin.Endocrinol.Metab.68. 787-795 (1989)
[文献書誌] Tashiro-Hashimoto,Y.: "Tyrosine-phosphorylation of pp185 by insulin receptor kinase in a cell-free system." J.Biol.Chem.264. 6879-6885 (1989)
[文献書誌] Odawara,M.: "Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor." Science. 245. 66-68 (1989)
[文献書誌] Zu,Y.: "Characterization of interleukin 2-stimulated 65KDa phosphoprotein in human T cells." Biochemistry.
[文献書誌] Kohno,M.: "Mitogenic signaling pathway of tumor mecrosis factor involves the rapid tyrosine phosphorylation of 41000-Mr and 43000-Mr cytosol proteins." Biochem.J.
[文献書誌] Akiko Miniwa: "Dephoshorylation of retinoblastoma gene products at the early stage of differentiation of human lymphoma U-937 cells." FEBS LETTERS.
[文献書誌] Ohtani,K.: "Electroporation;Application to human lymphoid cell lines for stable introduction of a transactivator gene of human T-cell leukemia virus type I." Nucleic Acids Res.17. 1589-1604 (1989)
[文献書誌] Nakamura,M.: "Differential activation of the 2i-base-pair enhancer element of human T-cell leukemia virus type I by its own trans-activator and cyclic AMP." Nucleic Acids Res.17. 5207-5221 (1989)
[文献書誌] Nagata,K.: "Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40^<tax> protein in the human T-cell line,Jurkat." J.Virol.63. 2422-2426 (1989)
[文献書誌] T.Akiyama: "Marked altriation in phosphorylation of the RB Protein during differentiation of human promyelocytic leukemia HL 60 cell." Oneogene. 5. 179-183 (1990)
[文献書誌] S.Mori: "In vitro and in vivo release of soluble erbB-2 protein from human carcinoma cills." Jpn.J.Cancer Res.
[文献書誌] M.Matsumoto: "Expression of Proto-oncogene products during druginduced differentiation of neuroblastoma cell line SK-N-DZ." Acta Neuropathologica. 79. 217-221 (1989)
[文献書誌] Honma,T.: "Inducyion of erythroid differentiation of K562 leukemic cells by herbimycin A,an inhibitor of tyrosine kinase activity." Cancer Res.49. 331-334 (1989)
[文献書誌] Uehara,Y.: "Mechanism of reversion fo Rous sarcoma virus transformation by herbimycin A;reduction of total phosphotyrosine levels due to reduced kinase activity and increased turnover of p60^<v-src>." Cancer Res.49. 780-785 (1989)
[文献書誌] Kondo,K.: "Induction of in vitro diffrentiation of mouse embryonal carcinoma(F9)and erythroleukemia(MEL)cells by herbimycin A,an inhibitor of protein phosphorylation." J.Cell Biol.109. 285-293 (1989)
[文献書誌] Namba,Y.: "A novel antigen expressed in the HTLV-I-infected cells detected with a monoclonal antibody.in Lymphold Malignancy;Immunocytology and Cytogenetics" Field and Wood Inc., 8 (1989)
[文献書誌] Nakamura,M.: "Reglation of the promoter activity of human T-cell leukemia Virus type I.in "Gene Transfer and Gene Therapy"" Alan R.Liss Inc., 14 (1989)
[文献書誌] T.Akiyama: "Use and specificity of genistein as inhibitor of protein tyrosine kinases." Methods in Enzymology,
[文献書誌] T.Yamamoto: "Oncogenic potential and normal function of the proto-oncogenes encoding protein-tyrosine kinases.In;"Mechanisms of Antimutagenesis and Anticarcinogenesis"" Plenum Publishing Corporation,
[文献書誌] S.Matsuda: "Regulation of expression and transforming ability of the c-erbB-2 gene.In Genetic Basis for Carcino-genesis;Tumor Suppressor Gene and Oncogenes" Japan Sci.Soi.,

1989 年度 実績報告書

発癌と細胞増殖制御におけるリン酸化チロシンタン白の役割

研究代表者

渡辺 泰 東海大学, 医学部, 教授 (60055746)

研究成果

[文献書誌] Makoto Nishizawa: "v-maf,a aviral oncogene that encodes a "leucine zipper"motif." Proc.Natl.Acad.Sci.USA. 86. 7711-7715 (1989)

[文献書誌] Sadaaki Kawai: "A Variant Schmidt-Ruppin Strain of Rous Sarcoma Virus with Increased Affinity for Mammalian Cells." Jpn.J.Cancer Res.80. 1179-1185 (1989)

[文献書誌] Kentaro Semba: "Transformation of Chicken Embryo Fibroblast Cells.by Avian Retoviruses containing the human Fyn gene and Its Mutated Genes." Mol.Cell.Biol.

[文献書誌] Takayama-Hasumi,S.: "Autoantibodies to the insulin(B-10)can stimulate tyrosine phosphorylation of the β-subunit of the insulin receptor and a 185,000 MW protein in rat hepatoma cells." J.Clin.Endocrinol.Metab.68. 787-795 (1989)

[文献書誌] Tashiro-Hashimoto,Y.: "Tyrosine-phosphorylation of pp185 by insulin receptor kinase in a cell-free system." J.Biol.Chem.264. 6879-6885 (1989)

[文献書誌] Odawara,M.: "Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor." Science. 245. 66-68 (1989)

[文献書誌] Zu,Y.: "Characterization of interleukin 2-stimulated 65KDa phosphoprotein in human T cells." Biochemistry.

[文献書誌] Kohno,M.: "Mitogenic signaling pathway of tumor mecrosis factor involves the rapid tyrosine phosphorylation of 41000-Mr and 43000-Mr cytosol proteins." Biochem.J.

[文献書誌] Akiko Miniwa: "Dephoshorylation of retinoblastoma gene products at the early stage of differentiation of human lymphoma U-937 cells." FEBS LETTERS.

[文献書誌] Ohtani,K.: "Electroporation;Application to human lymphoid cell lines for stable introduction of a transactivator gene of human T-cell leukemia virus type I." Nucleic Acids Res.17. 1589-1604 (1989)

[文献書誌] Nakamura,M.: "Differential activation of the 2i-base-pair enhancer element of human T-cell leukemia virus type I by its own trans-activator and cyclic AMP." Nucleic Acids Res.17. 5207-5221 (1989)

[文献書誌] Nagata,K.: "Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40^<tax> protein in the human T-cell line,Jurkat." J.Virol.63. 2422-2426 (1989)

[文献書誌] T.Akiyama: "Marked altriation in phosphorylation of the RB Protein during differentiation of human promyelocytic leukemia HL 60 cell." Oneogene. 5. 179-183 (1990)

[文献書誌] S.Mori: "In vitro and in vivo release of soluble erbB-2 protein from human carcinoma cills." Jpn.J.Cancer Res.

[文献書誌] M.Matsumoto: "Expression of Proto-oncogene products during druginduced differentiation of neuroblastoma cell line SK-N-DZ." Acta Neuropathologica. 79. 217-221 (1989)

[文献書誌] Honma,T.: "Inducyion of erythroid differentiation of K562 leukemic cells by herbimycin A,an inhibitor of tyrosine kinase activity." Cancer Res.49. 331-334 (1989)

[文献書誌] Uehara,Y.: "Mechanism of reversion fo Rous sarcoma virus transformation by herbimycin A;reduction of total phosphotyrosine levels due to reduced kinase activity and increased turnover of p60^<v-src>." Cancer Res.49. 780-785 (1989)

[文献書誌] Kondo,K.: "Induction of in vitro diffrentiation of mouse embryonal carcinoma(F9)and erythroleukemia(MEL)cells by herbimycin A,an inhibitor of protein phosphorylation." J.Cell Biol.109. 285-293 (1989)

[文献書誌] Namba,Y.: "A novel antigen expressed in the HTLV-I-infected cells detected with a monoclonal antibody.in Lymphold Malignancy;Immunocytology and Cytogenetics" Field and Wood Inc., 8 (1989)

[文献書誌] Nakamura,M.: "Reglation of the promoter activity of human T-cell leukemia Virus type I.in "Gene Transfer and Gene Therapy"" Alan R.Liss Inc., 14 (1989)

[文献書誌] T.Akiyama: "Use and specificity of genistein as inhibitor of protein tyrosine kinases." Methods in Enzymology,

[文献書誌] T.Yamamoto: "Oncogenic potential and normal function of the proto-oncogenes encoding protein-tyrosine kinases.In;"Mechanisms of Antimutagenesis and Anticarcinogenesis"" Plenum Publishing Corporation,

[文献書誌] S.Matsuda: "Regulation of expression and transforming ability of the c-erbB-2 gene.In Genetic Basis for Carcino-genesis;Tumor Suppressor Gene and Oncogenes" Japan Sci.Soi.,

1989 年度実績報告書

渡辺泰東海大学, 医学部, 教授 (60055746)