1999 Fiscal Year Annual Research Report

細胞間接着を制御するc-Srcキナーゼ依存伝達系の解析

Research Project

Project/Area Number	10670137
Research Institution	Nagoya University
Principal Investigator	浜口道成名古屋大学, 医学部, 教授 (90135351)
Co-Investigator(Kenkyū-buntansha)	松田覚名古屋大学, 医学部, 講師 (50242110)
Keywords	カドヘリン / Src-キナーゼ / シグナル伝達系 / 細胞間接着 / Ras / MAPキナーゼ
Research Abstract	本研究の主眼点は、シグナル伝達系によるカドヘリン依存性細胞間接着の可逆的な制御機構を生化学的に解明する事にある。我々は、Srcキナーゼのシグナル伝達系を解析し、この細胞間接着系がリン酸化を介するシグナル伝達系によって可逆的な制御を受けることを初めて明らかにした。これらの成果にもとづき本研究は、細胞周期依存の接着制御や、NO依存シグナル伝達系を主題として、細胞間接着系のSrcキナーゼ依存シグナル伝達系による制御機構を解析する事を立案した。本年の成果は、(1)Srcキナーゼと結合し、その活性化を促進するアダプター型シグナル伝達因子Crkが、Ras-Mek系を介してカドヘリン依存性細胞間接着を著明に制御する事を明らかにした。(2)我々は、重金属やNOなどの刺激がc-Srcキナーゼを活性化させることを初めて明かにした。そこで、Src導入細胞にeNOS遺伝子を導入し、相互反応を調べたところ、活性型SrcキナーゼとeNosが結合する事を見い出した。以上の成果は、Srcシグナル伝達系による可逆的な細胞接着制御機構を系統的・包括的理解する上で重要な知見となると確信している。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Serbulea,M.,Hamaguchi,M.et al.: "Hyaluronan activates mitogen-activated protein kinase via Ras-signaling pathway".Int J.Oncogene. 14. 733-738 (1999)
[Publications] Akhand,A.A.,Hamaguchi,M.et al: "Nitric oxide controls Src kinase activity through a redox-based molecular modification"J.Biol.Chem.. 274. 25821-25826 (1999)
[Publications] Thant,A.A.,Hamaguchi,M.: "Ras pathway is required for the activation of MMP-2 and for the invasion of src-transformed 3Y1"Oncogene. 18(47). 6555-6563 (1999)
[Publications] Itano,N.,Hamaguchi.,et al: "Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties"J.Biol.Chem.. 274. 25085-25092 (1999)
[Publications] Miyazaki,K.,Hamaguchi,M.: "Critical amino acid substitutions in the Src SH3 domain that convert c-Src to be oncogenic."Biochem.Bioph.Res.Co.. 263. 759-764 (1999)
[Publications] Okuda,T.,Hamaguchi,M.et al: "Molecular cloning of macrophin,a human homologue of Drosophila kakapo with a close structural similarity to plectin and dystrophin."Biochem.Bioph.Res.Co.. 264. 568-574 (1999)
[Publications] Kurata,K.,Hamaguchi,M.: "Constitutive activation of MAP kinase kinase (MEK1)is critical and sufficient for the activation of MMP-2."Exp.Cell Res.. 254. 180-188 (2000)
[Publications] Senga,T.Hamaguchi,M.: "Clustered cysteine residues in the kinase domain of v-Src : critical role for protein stability,cell transformation and sensitivity to herbimycin A"Oncogene. 19. 273-279 (2000)
[Publications] Matsuda,S.,Hamaguchi,M.: "Molecular cloning and characterization of a novel human gene(HERNA)which encodes a putative RNA-helicase"Biochem.Biophys.Acta. 1490. 163-169 (2000)
[Publications] Matsuda,S.,Hamaguchi,M.: "Molecular cloning and characterization of human MAWD,a novel protein containing WD-40 repeats frequently overexpressed in breast cancer"Cancer Res.. 60. 13-17 (2000)
[Publications] Machida,K.,Hamaguchi,M.: "v-Src suppresses SHP-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells"Oncogene. (in press).

1999 Fiscal Year Annual Research Report

細胞間接着を制御するc-Srcキナーゼ依存伝達系の解析

Principal Investigator

浜口 道成 名古屋大学, 医学部, 教授 (90135351)

Research Products

[Publications] Serbulea,M.,Hamaguchi,M.et al.: "Hyaluronan activates mitogen-activated protein kinase via Ras-signaling pathway".Int J.Oncogene. 14. 733-738 (1999)

[Publications] Akhand,A.A.,Hamaguchi,M.et al: "Nitric oxide controls Src kinase activity through a redox-based molecular modification"J.Biol.Chem.. 274. 25821-25826 (1999)

[Publications] Thant,A.A.,Hamaguchi,M.: "Ras pathway is required for the activation of MMP-2 and for the invasion of src-transformed 3Y1"Oncogene. 18(47). 6555-6563 (1999)

[Publications] Itano,N.,Hamaguchi.,et al: "Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties"J.Biol.Chem.. 274. 25085-25092 (1999)

[Publications] Miyazaki,K.,Hamaguchi,M.: "Critical amino acid substitutions in the Src SH3 domain that convert c-Src to be oncogenic."Biochem.Bioph.Res.Co.. 263. 759-764 (1999)

[Publications] Okuda,T.,Hamaguchi,M.et al: "Molecular cloning of macrophin,a human homologue of Drosophila kakapo with a close structural similarity to plectin and dystrophin."Biochem.Bioph.Res.Co.. 264. 568-574 (1999)

[Publications] Kurata,K.,Hamaguchi,M.: "Constitutive activation of MAP kinase kinase (MEK1)is critical and sufficient for the activation of MMP-2."Exp.Cell Res.. 254. 180-188 (2000)

[Publications] Senga,T.Hamaguchi,M.: "Clustered cysteine residues in the kinase domain of v-Src : critical role for protein stability,cell transformation and sensitivity to herbimycin A"Oncogene. 19. 273-279 (2000)

[Publications] Matsuda,S.,Hamaguchi,M.: "Molecular cloning and characterization of a novel human gene(HERNA)which encodes a putative RNA-helicase"Biochem.Biophys.Acta. 1490. 163-169 (2000)

[Publications] Matsuda,S.,Hamaguchi,M.: "Molecular cloning and characterization of human MAWD,a novel protein containing WD-40 repeats frequently overexpressed in breast cancer"Cancer Res.. 60. 13-17 (2000)

[Publications] Machida,K.,Hamaguchi,M.: "v-Src suppresses SHP-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells"Oncogene. (in press).

浜口道成名古屋大学, 医学部, 教授 (90135351)