1993 Fiscal Year Annual Research Report

細胞増殖・癌化のシグナル伝達とリン脂質代謝

Research Project

Project/Area Number	05151029
Research Institution	Gifu University
Principal Investigator	野澤義則岐阜大学, 医学部, 教授 (10021362)
Co-Investigator(Kenkyū-buntansha)	貝淵弘三神戸大学, 医学部, 助教授 (00169377) 千田和弘東京大学, 医科学研究所, 助手 (00192188) 浜口道成名古屋大学, 医学部, 教授 (90135351) 福井泰久東京大学, 農学部, 助教授 (00181248) 遠藤剛千葉大学, 理学部, 助教授 (30194038)
Keywords	細胞増殖 / 癌化シグナル / 情報伝達 / リン脂質代謝
Research Abstract	ras導入線維芽細胞の刺激によるCa^<2+>オシレーションに、膜電位およぴイノシトール四リン酸依存性チャンネルの関与が示された。細胞癌化に必須の不死化関連遺伝子mortalinをクローニングし、その抗体の細胞内注入はS期を誘導し細胞分裂をもたらした。ホスホリパーゼC_γ(PLC_γ)のSH2/SH3領域およびSH3領域のcDNAをマウス骨格筋細胞株C2に導入すると、c-junの誘導・分化の阻害がおこり、SH3領域の関与が示された。ホスファチジルイノシトール-3キナーゼ(P13K)はPC12細胞の神経突起の伸張に必要なことがわかった。α-アクチニンのN末側の各種合成ペプチドを用いてそのPIP_2結合部位を同定した。神経芽細胞腫癌組織の神経成長因子受容体(NGFR)の発現が著明に低下していた。表皮顆粒層に存在するnPKCηはコレステロール硫酸で活性化され、角化における重要性が示唆された。cdc2キナーゼによる各種中間経フィラメントのリン酸化における基質認識の一般的特性を解明した。Ras依存性にMAPキナーゼ・キナーゼ(MAPKK)を活性化する蛋白質REKSが、Rasと複合体を形成しMAPKKをリン酸化することを示した。化学発癌させたラット大腸癌のPLC_<δ1>の発現は対照に比べて減少していた。ジアシルグリセロールキナーゼのアイソザイムβ,γをクローニングし、その脳内分布を調べた。低分子量G蛋白質Rhoが細胞膜のラッフリングと細胞運動を制御することを解明した。トロンビン刺激血小板の細胞質型ホスホリパーゼA_2はMAPキナーゼによって活性化される可能性が示唆された。ラウス肉腫ウイルスで形質転換した細胞の収縮系蛋白質の集積したポドソームは、活発な運動性の物質的基盤であることを示した。Ras癌遺伝子関連フラット・リバータントの変異ゲルゾリンは、正常ゲルゾリンより著明にPLC_γ活性を抑制した。B細胞抗原受容体刺激により転写因子およびSH3構造を有するp75^<HSI>がチロシンリン酸化された。

Research Products

(32 results)

All Other

All Publications (32 results)

[Publications] Hashii,M.: "Bradykinin-induced cytosolic Ca^<2+> oscillations and inositol tetrakisphosphate-induced Ca^<2+> influx in voltage-clamped ras-transformed NIH/3T3 fibroblasts" J.Biol.Chem.268. 19403-19410 (1993)
[Publications] Koike,T.: "Stem cell factor-induced signal transduction in rat mast cells:Activation of phospholipase D but not phosphoinositide-specific phospholipase C in c-kit receptor stimulation" J.Immunol.151. 359-366 (1993)
[Publications] Wadhwa,R.: "Identification of a novel member of mouse hsp70 family.Its association with cellular mortal phenotype" J.Biol.Chem.268. 6615-6621 (1993)
[Publications] Wadhwa,R.: "Induction of cellular senescence by transfection of cytosolic mortalin cDNA in NIH3T3 cells" J.Biol.Chem.268. 22239-22242 (1993)
[Publications] Nakae,H.: "Ascidian entactin/nidogen:implication of evolution by shuffling two kinds of cysteine-rich motifs" Eur.J.Biochem.213. 11-19 (1993)
[Publications] Maruyama,K.: "A novel domain sequence of connenctin localized at the I band of skeletal muscle sarcomeres:homology to neurofilament subunits" Biochem.Biophys.Res.Commun.194. 1288-1291 (1993)
[Publications] Okada,T.: "Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase" J.Biol.Chem.(in press).
[Publications] Yano,H.: "Inhibition of histamine secretion by wortmannin through the blockage of phosphatidylinositol 3-kinase in RBL-2H3 cells" J.Biol.Chem.268. 25846-25856 (1993)
[Publications] Utsuyama,M.: "Influence of age on the signal transduction of T cells in mice" International Immunol.5. 1177-1182 (1993)
[Publications] Fukami,K.: "α-Actinin and vinculin are PIP_2-binding proteins involved in signaling by tyrosine kinase" J.Biol.Chem.269. 1518-1522 (1994)
[Publications] Yamanashi,Y.: "Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B cell antigen receptor-mediated singaling" Proc.Natl.Acad.Sci.USA. 90. 3631-3635 (1993)
[Publications] Choi,S.H.: "Expression of Lyn protein on human malignant lymphomas" Lab.Invest.69. 736-742 (1993)
[Publications] Hamaguchi,M.: "Herbimycin A inhibits the association of p60^<v-src> with the cytoskeletal structure and with phosphatidylinositol 3-kinase" Oncogene. 8. 559-564 (1993)
[Publications] Rahman,S.M.: "Redox-linked ligand-independent cell surface triggering for extensive protein tyrosine phosphorylation" FEBS Lett.317. 35-38 (1993)
[Publications] Yoshimi,N.: "One step procedure of PCR-DNA extraction from paraffin-embedded materials by Chelex-100" Acta Pathol.Jpn.43. 790-791 (1993)
[Publications] Yoshimi,N.: "Expression of cytokines,TNF-α and IL-1α,in MAM acetate and 1-hydroxyanthraquinone-induced colon carcinogenesis of rats" Carcinogenesis. (in press).
[Publications] Osada,S.: "Predominant expression of nPKCη,a Ca^<2+>-independent isoform of protein kinase C in epithelial tissues,in association with epithelial differentiation" Cell Growth & Differentiation. 4. 167-175 (1993)
[Publications] Kasahara,K.: "Rapid phosphorylation of 28-kDa heat shock protein by treatment with okadaic acid and phorbol ester of BALB/MK-2 mouse keratinocytes" Eur.J.Biochem.213. 1101-1107 (1993)
[Publications] Kusubata,M.: "cdc2 kinase phosphorylation of desmin at three serine/threonine residues in the amino-terminal head domain" Biochem.Biophys.Res.Commun.190. 927-934 (1993)
[Publications] Ando,S.: "Phosphorylation of synthetic vimentin peptides by cdc2 kinase" Biochem.Biophys.Res.Commun.195. 837-843 (1993)
[Publications] Itoh,T.: "A protein factor for ras p21-dependent activation of mitogen-activated protein(MAP)kinase through MAP kinase-kinase" Proc.Natl.Acad.Sci.USA. 90. 975-979 (1993)
[Publications] Orita,S.: "Comparison of kinetic properties between two mammalian ras p21 GDP/GTP exchange proteins,ras guanine nucleotide-releasing factor and smg GDP dissociation stimulator" J.Biol.Chem.268. 25542-25546 (1993)
[Publications] Hattori,A.: "Tumor necrosis factor stimulates the synthesis and secretion of biologically active nerve growth factor in non-neuronal cells" J.Biol.Chem.268. 2577-2582 (1993)
[Publications] Nakashima,S.: "Tyrosine phosphorylation and activation of mitogen-activated protein kinases by thrombin in human platelets:Possible involvement in late arachidonic acid release" Biochem.Biophys.Res.Commun.198. 497-503 (1994)
[Publications] Goto,K.: "Molecular cloning and expression of a 90kDa diacylglycerol kinase that predominantly localizes in neurons" Proc.Natl.Acad.Sci.USA. 90. 7598-7602 (1993)
[Publications] Goto,K.: "Molecular cloning and expression localization of two neuronal diacylglycerol(DG)kinase isozymes in rat brain" Neurosci.Res.suppl.18. S72 (1993)
[Publications] Sasaki,T.: "Consequences of weak interaction of rho GDI with the GTP-bound forms of rho p21 and rac p21" J.Biol.Chem.268. 23959-23963 (1993)
[Publications] Nishiyama,T.: "Rac p21 and Rho p21 are involved in the insulin-induced and HGF-and TPA-induced membrane rufflings,respectively,in KB cells" Mol.Cell.Biol.(in press).
[Publications] Tanaka,J.: "Morphological and biochemical analyses of contractile proteins(actin,myosin,caldesmon and tropomyocin)in normal and transformed cells" J.Cell Sci.104. 595-606 (1993)
[Publications] Nakamura,N.: "Rous sarcoma virus-transformed cells develop peculiar adhesive structures along the cell periphery" J.Cell Sci.106. 1057-1069 (1993)
[Publications] Mullauer,L.: "Tumor suppressive function of mutated gelsolin in ras-transformed cells" Oncogene. 8. 2531-2536 (1993)
[Publications] Katabami,M.: "Marked reduction of type I keratin(K14)in cisplatin-resistant human lung squamous-carcinoma cell lines" Biochem.Pharmacol.45. 1703-1710 (1993)

1993 Fiscal Year Annual Research Report

細胞増殖・癌化のシグナル伝達とリン脂質代謝

Principal Investigator

野澤 義則 岐阜大学, 医学部, 教授 (10021362)

Research Products

[Publications] Hashii,M.: "Bradykinin-induced cytosolic Ca^<2+> oscillations and inositol tetrakisphosphate-induced Ca^<2+> influx in voltage-clamped ras-transformed NIH/3T3 fibroblasts" J.Biol.Chem.268. 19403-19410 (1993)

[Publications] Koike,T.: "Stem cell factor-induced signal transduction in rat mast cells:Activation of phospholipase D but not phosphoinositide-specific phospholipase C in c-kit receptor stimulation" J.Immunol.151. 359-366 (1993)

[Publications] Wadhwa,R.: "Identification of a novel member of mouse hsp70 family.Its association with cellular mortal phenotype" J.Biol.Chem.268. 6615-6621 (1993)

[Publications] Wadhwa,R.: "Induction of cellular senescence by transfection of cytosolic mortalin cDNA in NIH3T3 cells" J.Biol.Chem.268. 22239-22242 (1993)

[Publications] Nakae,H.: "Ascidian entactin/nidogen:implication of evolution by shuffling two kinds of cysteine-rich motifs" Eur.J.Biochem.213. 11-19 (1993)

[Publications] Maruyama,K.: "A novel domain sequence of connenctin localized at the I band of skeletal muscle sarcomeres:homology to neurofilament subunits" Biochem.Biophys.Res.Commun.194. 1288-1291 (1993)

[Publications] Okada,T.: "Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase" J.Biol.Chem.(in press).

[Publications] Yano,H.: "Inhibition of histamine secretion by wortmannin through the blockage of phosphatidylinositol 3-kinase in RBL-2H3 cells" J.Biol.Chem.268. 25846-25856 (1993)

[Publications] Utsuyama,M.: "Influence of age on the signal transduction of T cells in mice" International Immunol.5. 1177-1182 (1993)

[Publications] Fukami,K.: "α-Actinin and vinculin are PIP_2-binding proteins involved in signaling by tyrosine kinase" J.Biol.Chem.269. 1518-1522 (1994)

[Publications] Yamanashi,Y.: "Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B cell antigen receptor-mediated singaling" Proc.Natl.Acad.Sci.USA. 90. 3631-3635 (1993)

[Publications] Choi,S.H.: "Expression of Lyn protein on human malignant lymphomas" Lab.Invest.69. 736-742 (1993)

[Publications] Hamaguchi,M.: "Herbimycin A inhibits the association of p60^<v-src> with the cytoskeletal structure and with phosphatidylinositol 3-kinase" Oncogene. 8. 559-564 (1993)

[Publications] Rahman,S.M.: "Redox-linked ligand-independent cell surface triggering for extensive protein tyrosine phosphorylation" FEBS Lett.317. 35-38 (1993)

[Publications] Yoshimi,N.: "One step procedure of PCR-DNA extraction from paraffin-embedded materials by Chelex-100" Acta Pathol.Jpn.43. 790-791 (1993)

[Publications] Yoshimi,N.: "Expression of cytokines,TNF-α and IL-1α,in MAM acetate and 1-hydroxyanthraquinone-induced colon carcinogenesis of rats" Carcinogenesis. (in press).

[Publications] Osada,S.: "Predominant expression of nPKCη,a Ca^<2+>-independent isoform of protein kinase C in epithelial tissues,in association with epithelial differentiation" Cell Growth & Differentiation. 4. 167-175 (1993)

[Publications] Kasahara,K.: "Rapid phosphorylation of 28-kDa heat shock protein by treatment with okadaic acid and phorbol ester of BALB/MK-2 mouse keratinocytes" Eur.J.Biochem.213. 1101-1107 (1993)

[Publications] Kusubata,M.: "cdc2 kinase phosphorylation of desmin at three serine/threonine residues in the amino-terminal head domain" Biochem.Biophys.Res.Commun.190. 927-934 (1993)

[Publications] Ando,S.: "Phosphorylation of synthetic vimentin peptides by cdc2 kinase" Biochem.Biophys.Res.Commun.195. 837-843 (1993)

[Publications] Itoh,T.: "A protein factor for ras p21-dependent activation of mitogen-activated protein(MAP)kinase through MAP kinase-kinase" Proc.Natl.Acad.Sci.USA. 90. 975-979 (1993)

[Publications] Orita,S.: "Comparison of kinetic properties between two mammalian ras p21 GDP/GTP exchange proteins,ras guanine nucleotide-releasing factor and smg GDP dissociation stimulator" J.Biol.Chem.268. 25542-25546 (1993)

[Publications] Hattori,A.: "Tumor necrosis factor stimulates the synthesis and secretion of biologically active nerve growth factor in non-neuronal cells" J.Biol.Chem.268. 2577-2582 (1993)

[Publications] Nakashima,S.: "Tyrosine phosphorylation and activation of mitogen-activated protein kinases by thrombin in human platelets:Possible involvement in late arachidonic acid release" Biochem.Biophys.Res.Commun.198. 497-503 (1994)

[Publications] Goto,K.: "Molecular cloning and expression of a 90kDa diacylglycerol kinase that predominantly localizes in neurons" Proc.Natl.Acad.Sci.USA. 90. 7598-7602 (1993)

[Publications] Goto,K.: "Molecular cloning and expression localization of two neuronal diacylglycerol(DG)kinase isozymes in rat brain" Neurosci.Res.suppl.18. S72 (1993)

[Publications] Sasaki,T.: "Consequences of weak interaction of rho GDI with the GTP-bound forms of rho p21 and rac p21" J.Biol.Chem.268. 23959-23963 (1993)

[Publications] Nishiyama,T.: "Rac p21 and Rho p21 are involved in the insulin-induced and HGF-and TPA-induced membrane rufflings,respectively,in KB cells" Mol.Cell.Biol.(in press).

[Publications] Tanaka,J.: "Morphological and biochemical analyses of contractile proteins(actin,myosin,caldesmon and tropomyocin)in normal and transformed cells" J.Cell Sci.104. 595-606 (1993)

[Publications] Nakamura,N.: "Rous sarcoma virus-transformed cells develop peculiar adhesive structures along the cell periphery" J.Cell Sci.106. 1057-1069 (1993)

[Publications] Mullauer,L.: "Tumor suppressive function of mutated gelsolin in ras-transformed cells" Oncogene. 8. 2531-2536 (1993)

[Publications] Katabami,M.: "Marked reduction of type I keratin(K14)in cisplatin-resistant human lung squamous-carcinoma cell lines" Biochem.Pharmacol.45. 1703-1710 (1993)

野澤義則岐阜大学, 医学部, 教授 (10021362)