1989 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	01010062
Research Institution	Tokai University
Principal Investigator	渡辺泰東海大学, 医学部, 教授 (60055746)
Co-Investigator(Kenkyū-buntansha)	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)
Keywords	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
Research Abstract	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。

Research Products
(23 results)

All Other

All Publications (23 results)

[Publications] Makoto Nishizawa: "v-maf,a aviral oncogene that encodes a "leucine zipper"motif." Proc.Natl.Acad.Sci.USA. 86. 7711-7715 (1989)
[Publications] 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)
[Publications] Kentaro Semba: "Transformation of Chicken Embryo Fibroblast Cells.by Avian Retoviruses containing the human Fyn gene and Its Mutated Genes." Mol.Cell.Biol.
[Publications] 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)
[Publications] Tashiro-Hashimoto,Y.: "Tyrosine-phosphorylation of pp185 by insulin receptor kinase in a cell-free system." J.Biol.Chem.264. 6879-6885 (1989)
[Publications] Odawara,M.: "Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor." Science. 245. 66-68 (1989)
[Publications] Zu,Y.: "Characterization of interleukin 2-stimulated 65KDa phosphoprotein in human T cells." Biochemistry.
[Publications] Kohno,M.: "Mitogenic signaling pathway of tumor mecrosis factor involves the rapid tyrosine phosphorylation of 41000-Mr and 43000-Mr cytosol proteins." Biochem.J.
[Publications] Akiko Miniwa: "Dephoshorylation of retinoblastoma gene products at the early stage of differentiation of human lymphoma U-937 cells." FEBS LETTERS.
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] T.Akiyama: "Marked altriation in phosphorylation of the RB Protein during differentiation of human promyelocytic leukemia HL 60 cell." Oneogene. 5. 179-183 (1990)
[Publications] S.Mori: "In vitro and in vivo release of soluble erbB-2 protein from human carcinoma cills." Jpn.J.Cancer Res.
[Publications] M.Matsumoto: "Expression of Proto-oncogene products during druginduced differentiation of neuroblastoma cell line SK-N-DZ." Acta Neuropathologica. 79. 217-221 (1989)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] T.Akiyama: "Use and specificity of genistein as inhibitor of protein tyrosine kinases." Methods in Enzymology,
[Publications] T.Yamamoto: "Oncogenic potential and normal function of the proto-oncogenes encoding protein-tyrosine kinases.In;"Mechanisms of Antimutagenesis and Anticarcinogenesis"" Plenum Publishing Corporation,
[Publications] 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 Fiscal Year Annual Research Report

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

Principal Investigator

渡辺 泰 東海大学, 医学部, 教授 (60055746)

Research Products

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

[Publications] 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)

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

[Publications] 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)

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

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

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

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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.,

渡辺泰東海大学, 医学部, 教授 (60055746)