1995 Fiscal Year Annual Research Report

細胞内情報伝達機構網の研究

Research Project

Project/Area Number	07NP0901
Research Institution	Kobe University
Principal Investigator	西塚泰美神戸大学, 学長 (10025546)
Co-Investigator(Kenkyū-buntansha)	横山光宏神戸大学, 医学部, 教授 (40135794) 淀井淳司京都大学, ウイルス研究所, 教授 (80108993) 福井泰久東京大学, 農学部, 教授 (00181248) 山村博平神戸大学, 医学部, 教授 (90030882) 井上圭三東京大学, 薬学部, 教授 (30072937)
Keywords	ホスファチジルイノシトール3キナーゼ / ホスホリパーゼC / ホスホリパーゼD / チロシンキナーゼ / 低分子量G蛋白質 / 核局在化シグナル / ADF / チオレドキシン / 一酸化窒素
Research Abstract	細胞内情報伝達機構網の詳細の解明をめざし、総括班および6研究班を組織し、総括班は研究計画の統合推進を担当し、全体会議を開催し研究班間の円滑な交流、連絡をはかった。6研究班は以下の成果を収めた。 1.研究班1: 脳の酸化リン脂質/PAF特異的ホスホリパーゼA2をクローニングし、脳形態形成に重要であることを見いだした。ホスホリパーゼDを粘菌から部分精製し、モノクロナール抗体を作製した。ホスホリパーゼDがHL60細胞では低分子量G蛋白質rho、ARFにより活性化され、CD14発現CHO細胞ではCD14を介するリポポリサッカライド刺激伝達へ関与することを示した。TNFαによるシクロオキシゲナーゼ-2誘導がNF_KBとNF-IL6の協調作用により転写調節を受けることを示した。トロンビン刺激等によるカルシウム動員調節にミトコンドリアが関与する結果を得た。分裂細胞の分裂溝でリン脂質の活発なフリップ-フロップが起こり、リン脂質の動きを制止することにより細胞分裂の進行が阻害されることが示され、膜リン脂質分子の細胞分裂の制御因子としての新たな機能が見いだされた。 2. 研究班2: チロシンキナーゼSykがオキシダントや放射線刺激により活性化されることを明らかにし、サイクリックAMP系がSykの活性化に阻害的に作用することを示した。中枢神経系での長期抑圧への関与が指摘されるAMPA受容体がLynと会合し、AMPA刺激によりLynの自己リン酸化が上昇しAMPA受容体がLynによりリン酸化されることを示した。低分子量G蛋白質Rhoの標的蛋白質としてPKN(protein kinase N)、p160ROCK等を同定した。低分子量G蛋白質RacおよびCdc42の標的蛋白質としてホスファチジルイノシトール3キナーゼとIQGAPを同定した。再生肝cDNAライブラリーより核内に存在し細胞周期のS期に誘導される新規ホスホリパーゼCをクローニングした。 3. 研究班3: PHドメインを持つRACプロテインキナーゼがプロテインキナーゼC分子種と結合し、細胞刺激により両者の結合が増強されることを示した。ラット組織よりPKNの精製方法を確立しその酵素化学解析を行った。従来から知られているホスホリパーゼCによるプロテインキナーゼCの活性化経路に加え、ホスファチジルイノシトール3キナーゼを介する経路の存在を見いだし、ホ … More スファチジルイノシトール3キナーゼ経路の下流因子として知られるS6キナーゼがプロテインキナーゼCλ分子種と直接結合することを見いだした。癌抑制遺伝子産物APCおよびMCCが細胞周期のG0/G1期からS期への進行を制御することを明らかにした。代謝性グルタミン酸受容体刺激によるNMDA受容体の感受性増強反応には、カルシウム非依存性プロテインキナーゼC分子種が関与することを示した。 4. 研究班4: 核蛋白質の核膜への移行に際して細胞質で形成される「核膜孔ターゲティング複合体」の必須構成因子のうち、PTAC58およびPTAC97の精製とクローニングに成功し、前者は核蛋白質の核局在化シグナルを認識し、後者はそれらを核膜まで運ぶのに必要な因子であることを示した。プロテインキナーゼCη分子種を活性化するコレステロール硫酸がケラチノサイトのトランスグルタミナーゼ遺伝子の転写を促進し、アデノウィルスベルターを用いたプロテインキナーゼCη分子種過剰発現によりケラチノサイトの細胞分化とトランスグルタミナーゼ転写が誘導されることを示した。ホスファチジルイノシトール3、4、5三リン酸のアナログを用いたアフィニティークロマトグラフィーによりその特異的結合蛋白質を精製し、部分アミノ酸配列決定により新規蛋白質であることを明らかにした。分裂酵母のホスファチジルイノシトール3キナーゼ遺伝子破壊により接合能と胞子形成能の低下、G1アレスト阻害が起こることを示した。膜結合型ヘパリン結合性EGF様増殖因子のヘパリン結合ドメインがCD9のGlu139-Ala158と結合することを明らかにした。 5. 研究班5: 酵母Two-hybrid系によるADF/チオレドキシン会合分子の検索により食細胞のoxygen burstに関与するphox40を同定した。プロB細胞においてsrcファミリーの一つであるfynが細胞分裂後期にmidbodyに濃縮されミオシン活性化に関わり、分裂溝のアクチンとミオシンが反応して最終の分裂プロセスが進行することを明らかにした。抗Fasモノクローナル抗体カラムを用いて分子量90kdの蛋白質を精製し、その部分アミノ酸配列決定により既知蛋白質ではないことを示した。炎症性乳癌患者の生検材料をヌードマウスに移植し、移植可能なマウス由来のTNK細胞株を樹立し、同時にin vitroで培養可能なTNK細胞株を樹立した。 6. 研究班6: 血管内皮細胞の一酸化窒素合成酵素の活性にはそのアミノ末端のミリスチン化による細胞膜への結合および各種脂質環境が重要であることが判明した。動脈硬化血管においては血管内皮細胞一酸化窒素合成酵素の発現が増大しており、その機序として酸化LDLやサイトカインが関与していることを見いだした。エンドセリン受容体に共役するGタンパク質の特異性を明らかにした。ラット大動脈初代培養血管平滑筋細胞の細胞周期制御において、高グルコースとインスリンがG1期からS/M期へのカルシウム非依存性プログレッション増殖因子であることを明らかにした。リゾホスファチジルコリンによる血管内皮細胞での接着因子遺伝子発現の際に分子量130kDの蛋白質が速やかにチロシンリン酸化を受けることを見いだした。 Less

Research Products

(112 results)

All Other

All Publications (112 results)

[Publications] Inoue, H.: "Potential role of protein phosphorylation in GTP-γ-Sdependent activation of phospholipase D." Biochem. Biophys. Res. Commun.210. 542-548 (1995)
[Publications] Yamaguchi, K.: "The protein kinase C isoforms leading to MAP-kinase activation in CHO cells." Biochem. Biophys. Res. Commun.210. 639-647 (1995)
[Publications] Nakamura, S.: "Mammalian phospholipase D: Activation by ammonium sulfate and nucleotides." Proc. Natl. Acad. Sci. USA. 92. 12319-12322 (1995)
[Publications] Nakamura, S.: "Mammalian phospholipase D: Phosphatidylethanolamine as an essential component." Proc. Natl. Acad. Sci. USA. (in press).
[Publications] Sato, K-I.: "Site-specific association of c-Src with epidermal growth factor receptor in A431 cells." Biochem. Biophys. Res. Commun.210. 844-851 (1995)
[Publications] Sato, K-I.: "c-Src phosphorylates epidermal growth factor receptor on tyrosine-845." Biochem. Biophys. Res. Commun.215. 1078-1087 (1995)
[Publications] Sahara, S.: "Biochemical evidence for the interaction of regulatory subunit of cAMP-dependent protein kenase with IDA(Inter-DFG-APE)region of catalytic subunit." FEBS Lett.(in press). (1996)
[Publications] Sato, K-I.: "Purification and characterization of a Src-related p57 protein-tyrosine kinase from Xenopus oocytes: Isolation of an inactive form of the enzyme, and its activation and traslocation upon fertilization." J. Biol. Chem.(in press). (1996)
[Publications] Deng-Shun Wang: "Binding of pleckstrin homology domains to WD40/β-transducin repeat containing segments of the protein product of the Lis-1 gene" Biochem. Biophys. Res. Communi.209. 622-629 (1995)
[Publications] Kakutani Yokoyama: "Phospholipid degradation in rat calcium ionophore-activated platelets is catalyzed mainly by two discrete secretory phospholipase As" J. Biochem.117. 1280-1287 (1995)
[Publications] Kenji Hattori: "Purification and characterization of platelet-activating factor acetylhydrolase II from bovine liver cytosol" J. Biol. Chem.270. 22308-22313 (1995)
[Publications] Hideki Adachi: "cDNA cloning of human cytosolic platelet-activating factor acetylhydrolase g-subunit and its mRNA expression in human tissues" Biochem. Biophys. Res. Communi.214. 180-187 (1995)
[Publications] Mitsuharu Hattori: "Cloning and expression of a cDNA encoding the b-subunit(30-kDa subunit)of bovine brain platelet-activating factor acetylhydrolase" J. Biol. Chem.270. 31345-31352 (1995)
[Publications] Yamamoto, K.: "Transcriptional roles of nuclear factor κB and nuclear factor-interleukin-6 in the tumor necrosis factor α-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells" J. Biol. Chem.(in press).
[Publications] Endo, T.: "Induction of cyclooxygenase-2 is responsible for interleukin-1β-dependent prostaglandin E2 synthesis by human lung fibroblasts" Am. J. Respir. Cell Mol. Biol.12. 358-365 (1995)
[Publications] Ohtsuki, T.: "Reperfusion induces 5-lipoxygenase translocation and leukotriene C_4 production in ischemic brain" Am. J. Physiol.268. H1249-1257 (1995)
[Publications] Nakamura, M.: "Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase in mouse blood cells" J. Histochem. Cytochem.43. 237-244 (1995)
[Publications] Arakawa, T.: "The transcriptional regulation of human arachidonate 12-lipoxygenase gene by NFkB/Rel" FEBS Lett.363. 105-110 (1995)
[Publications] Ueda, N.: "Oxygenation of arachidonylethanolamide(anadamide)by lipoxygenases" Advances in Prostaglandin, Thromboxane, and Leukotriene Research. 23. 163-165 (1995)
[Publications] Katori, M.: "Induction of prostaglandin H synthase-2 in rat carrageenin-induced pleurisy and effect of a selective COX-2 inhibitor" Advances in Prostaglandin, Thromboxane, and Leukotriene Research. 23. 345-347 (1995)
[Publications] Alam, S: "Defective phospholipase D activation in Ki-ras-tansformed NIH3T3 cells: Evidence for downstream effect of PLC-γ1" Biochem. Biophys. Res. Commun.207. 460-466 (1995)
[Publications] Banno, Y.: "Endogenous cleavage of phospholipase Cβ3 by agonist-induced activation of calpain in human platelets" J. Biol. Chem.270. 4318-4323 (1995)
[Publications] Nakamura, Y.: "Effects of an anti allergic drug, permirolast potassium on tyrosine phosphorylation and MAP kinase activation in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells" Jpn. J. Allergol.44. 34-44 (1995)
[Publications] Nagata, K.: "Possible interaction of hemoglobin with a low Mr GTP-binding protein ram p25" Biochem. Mol. Biol. Int.35. 507-515 (1995)
[Publications] Fujita, H.: "Functions of mutant gelsolin, His 321 isolated from a flat revertant of Ras-transformed cells" Eur. J. Biochem.229. 615-620 (1995)
[Publications] Nagata, K.: "A low molecular GTP-binding protein, Rap1, in human platelets: Locali-zation, translocation and phosphorylation by cyclic AMP-dependent protein kinase" Brit. J. Haematol.90. 180-186 (1995)
[Publications] Ohguchi, K.: "Activation of membrane-bound phospholipase D by protein kinase C in HL-60 cells: Synergistic action of a small GTP-binding protein RhoA" Biochem. Biophys. Res. Commun.211. 306-311 (1995)
[Publications] Nakashima, S.: "Delection and site-directed mutagenesis of EF-hand domain of phospholipase C-delta 1: Effects on its activity" Biochem. Biophys. Res. Commun.211. 364-369 (1995)
[Publications] Adachi, T.: "Roles of prostaglandin production and MAP kinase activation in hepatocyte growth factor-meiated rat hepatocyte proliferation" Hepatology. 21. 1668-1874 (1995)
[Publications] Kumada, T.: "Antigen-mediated phospholipase D activation in rat basophilic leukemia(RBL-2H3)cells: Involvement of calcium/calmodulin" Biochim. Biophys. Acta. 1258. 107-114 (1995)
[Publications] Liu, B.: "Implication of protein kinase Cα in PAF-stimulated phospholipase D(PLD)activation in Chinese hamster ovary(CHO)cells expressing PAF receptor" Biochem. Biophys. Res. Commun.214. 418-423 (1995)
[Publications] Nagata, K.: "Identification of heterotrimeric GTP-binding proteins in human megakaryoblastic leukemia cell, MEG-O1, and their alteration during cellular differentiation" Life Sci.57. 1675-1681 (1995)
[Publications] Nakamura, Y.: "C2-ceramide inhibits IgG-mediated phospholipase D but not C activation in rat basophilic leukemia(RBL-2H3)cells" J. Immunol.156. 256-262 (1996)
[Publications] Ohguchi, K.: "Regulation of membrane-bound phospholipase D by protein kinase C in HL-60 cells: Synergistic action of small GTP-binding protein RhoA" J. Biol. Chem.271. 4366-4373 (1996)
[Publications] Nagata, K.: "Identification and localization of gene expression of a low Mr GTP-binding protein, Ram p25 in pituitary gland" Biochem. Biophys. Res. Commun.217. 1223-1230 (1996)
[Publications] Adachi, T.: "Mitogen-activated protein kinase activation in hepatocyte growth factor-stimulated rat hepatocytes: Involvement of protein tyrosine kinase and protein kenase C" Hepatology. (in press).
[Publications] Kentarou Hanada: "Both Sphingolipids and Cholesterol Participate in the Detergent Insolubility of Alkaline Phosphatase, a Glycosylphosphatidylinositol-anchored Protein, in Mammalian Membranes" J. Biol. Chem.270. 6254-6260 (1995)
[Publications] Masao Shiozaki: "Syntheses of 1-0-[5-(Carboxy)pentanoyl]-2-deoxy-2-(2,2-dif-luorotetradecanamido)-3-0-[(R)-3-(tetradecanoyloxy)tetradecanoyl]-4-0-phosphono-α-D-gllucopyranose and Its Analogues" Biosci. Biotech. Biochem.59. 501-506 (1995)
[Publications] Jinhua Xu: "Identification of a Hemocyte Membrane Protein of the Silkworm, Boabyx mori, Which Specifically Binds to Bacterial Lipopoly-saccharide" Insect Biochem. Molec. Biol.25. 921-928 (1995)
[Publications] Igarashi, K.: "A novel phosphatidylserine-binding peptide motif defined by an anti-idiotypic momoclonal antibody: Localization of phosphatidylserine-specific binding sites on protein kinase C and phosphatidylserine decarboxylase." J. Biol. Chem.270. 29075-29078 (1995)
[Publications] Igarashi, K.: "Specific binding of a synthetic peptide derived from an antibody complementarity determining region to phosphatidylserine." J. Biochem.117. 452-457 (1995)
[Publications] Tokita, S.: "Specific cross-reaction of IgG anti-phospholipid antibody with platelet glycoprotein IIIa." Thromb. Haemost.75. 168-174 (1996)
[Publications] Nagai, K. et al.: "Tyrosine phosphorylation of Shc is mediated through Lyn and Syk in B cell receptor signaling." J. Biol. Chem.270(12). 6824-6829 (1995)
[Publications] Yanagi, S. et al.: "The structure and function of p72^<syk> expressed in hematopoietic cells21GC01:Cellular Signalling" 7(3). 185-193 (1995)
[Publications] Qin, S. et al.: "Activation and tyrosine phosphorylation of p72^<syk> as well as calcium mobilization after hydrogen peroxide stimulation in peripheral blood lymphocytes." Biochem. J.308(1). 347-352 (1995)
[Publications] Hirasawa, N.: "A requirement for syk in the activation of the microtubule-associated protein kinase/phospholipase A2 pathway by FceRl is not shared by a G protein-coupled receptor." J. Biol. Chem.270. 10960-10967 (1995)
[Publications] Ozaki, Y.: "Anti-CD9 monoclonal antibody activates p72syk in human platelets" J. Biol. Chem.270. 15119-15124 (1995)
[Publications] Maeda, H.: "Possible involvement of protein-tyrosine kinases such as p72syk in the Disc-Sphere change response of porcine platelets." J. Biochem.117. 1201-1208 (1995)
[Publications] Yang, C.: "Syk and Lyn are involved in radiation-induced signaling, but inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis." J. Biochem.118. 33-38 (1995)
[Publications] Asahi, M.: "Cyclic AMP-elevating agents negatively regulate the activation of p72syk in N-formyl-methionyl-leucyl-phenylalanine receptor signaling." Biophys. Biochem. Res. Commun.212. 887-893 (1995)
[Publications] Scharenberg, A. M.: "Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering." EMBO J.14. 3385-3394 (1995)
[Publications] Hashimoto, E.: "Purification and phosphorylation of Mr 25,000 protein, an effective phosphate acceptor for casein kinase II and protein kinase C, detected in the cytosolic fraction of Xenopus laevus oocytes." J. Biol. Chem.118. 453-460 (1995)
[Publications] Ichinohe, T.: "Cyclic AMP-insensitive activation of c-Src and Syk protein-tyrosine kinases through platelet membrane glycoprotein VI." J. Biochem.270. 28029-28036 (1995)
[Publications] Zeng, H.: "Phosphorylation of HSl, GAP-associated p190 and a novel GAP-associated p60 protein by cross-linking of FcgRIIIA." J. Biochem.118. 1166-1174 (1995)
[Publications] Kurosaki, T.: "Syk recruitment to Ig-a and its phosphorylation are essential for B cell antigen receptor signaling." J. Exp. Med.(in press). (1996)
[Publications] S. Shimihama, G. Perry, P. Richey, D. Praprotnik, T. Takenawa, K. Fukami, P. J. Whitehouse, J. Kimura: "Characterization of the association of phospholipase C-d with Alzheimer neurofibrillary tangles" Brain Research. 669. 217-224 (1995)
[Publications] J. C. Hay, P. L. Fisette, G. H. Jenkins, K. Fukami, T. Takenawa, R. A. Anderson and T. F. J. Martin: "ATP-dependent inositide phosphorylation required for Ca2+-activated secretion" Nature. 374. 173-177 (1995)
[Publications] H. Hosoya, K. Shimazaki, S. Kobayashi, H. Takahashi, T. Shirosawa, T. Takenawa and K. Watanabe: "Developmental expression of the neural adhesion molecule F3 in the rat brain" Neuroscience Lett.186. 83-86 (1995)
[Publications] K. Watanabe, T. Fukuchi, H. Hosoya, T. Shirosawa, K. Matuoka, H. Miki and T. Takenawa: "Splicing isoforms of rat Ash/Grb2: Isolation and characterization of the cDNA and genomic DNA clones and implications for the physiological roles of the isoforms" J. Biol. Chem.270. 13733-13739 (1995)
[Publications] Dusko, I.: "Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice" Nature. 377. 539-544 (1995)
[Publications] Tokai, N.: "Kid, a novel kinesin-like DNA binding protein, is colocalized with the chromosomes during mitosis" EMBO J.(in press).
[Publications] Nishizumi, H.: "Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice" Immunity. 3. 549-560 (1995)
[Publications] Kuramochi, S.: "Molecular cloning and characterization of Byp, a murine receptor-type tyrosine phosphatase similar to human DEP-1" FEBS Letters. (in press).
[Publications] Kuroda, S.: "Purification and characterization of REKS from Xenopus eggs-Identification of REKS as a Ras-dependent mitogen-activated kinase kinase kinase." J. Biol. Chem.270. 2460-2465 (1995)
[Publications] Yamamoto, T.: "A novel GTPase-activating protein for R-ras, R-Ras GAP." J. Biol. Chem.270. 30557-30561 (1995)
[Publications] Gotoh, T.: "Identification of Rapl as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G." Mol. Cell. Biol.15. 6746-6753 (1995)
[Publications] Miyazaki, M.: "Rabphilin-3A binds to a Mr 115,000 polypeptide in phosphatidylserine-and Ca^<2+> dependent manner." Mol. Brain Res.28. 29-36 (1995)
[Publications] Amano, K.: "Identification of a putative target for Rho as a serine-threonine kinase protein kinase N." Science. 271. 648-651 (1996)
[Publications] Kuriyama, M.: "Identification of AF-6 and Canoe as putative targets for Ras." J. Biol. Chem.271. 607-610 (1996)
[Publications] Matsui, T.: "Rho-associated kinase, a novel serine/threonine kinase, as a putative target for the small GTP-binding protein Rho." EMBO J.(in press).
[Publications] Kumagai, N., et al.: "Lysophosphatidic acid-induced activation of protein ser/thr kinases in cultured rat 3Yl fibroblasts: possible involvement in rho p21-mediated signalling." FEBS Letters.366. 11-16 (1995)
[Publications] Seckl, M. J., et al.: "Guanosine 5′-3-O-(thio)triphosphate stimulates tyrosine phosphorylation of p125^<FAK> and paxillin in permeabilized Swiss 3T3 cells." Journal of Biological Chemistry.270. 6984-6990 (1995)
[Publications] Madaule, P., et al.: "A novel partner for the GTP-bound forms of rho and rac." FEBS Letters.377. 243-248 (1995)
[Publications] Watanabe, G., et al.: "Protein kinase N(PKN)and PKN-related protein rhophilin as targets of small GTPase Rho." Science. 271. 645-648 (1996)
[Publications] Ishizaki, T., et al.: "The small GTP-binding protein Rho binds to and activates a 160kDA Ser/Thr protein kinase homologous to myotonic dystrophy kinase." EMBO. J.(in press).
[Publications] Reid, T., et al.: "Rhotekin, a new Rho target protein bearing homology to a serine threonine kinase, PKN, and rhophilin in the Rho binding domain." J. Biol. Chem.(in press).
[Publications] Konishi, H.: "Molecular cloning and characterization of a new member of the RAC protein kinase family: association of the pleckstrin homology domain of three types of RAC protein kinase with protein kinase C subspecies and βγ subunits of G proteins." Biochem. Biophys. Res. Commun.216. 526-534 (1995)
[Publications] Kasahara, K.: "Distinct effects of saturated fatty acids on protein kinase C subspecies." J. Biochem.117. 648-653 (1995)
[Publications] Oka, M.: "Differential down-regulation of protein kinase C subspecies in normal human melanocytes: possible involvement of the ζ subspecies in growth regulation." J. Invest. Dermatol.105. 567-571 (1995)
[Publications] Nakamura, F.: "Characterization of Gq family G proteins GL1α(G14α), GL2α(G11α), and Gqα expressed in the baculovirus-infected cell system." J. Biol. Chem.270. 6246-6253 (1995)
[Publications] Haga, K.: "Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kianse C." J. Biol. Chem.271. 2776-2782 (1996)
[Publications] Oka, M.: "Deletion of specific protein kinase C subspecies in human melanoma cells." J. Cell. Physiol.(in press). (1996)
[Publications] Kitagawa, M.: "Purification and characterization of a fatty acid-activated protein kinase(PKN)from rat testis." Biochem. J.310. 657-664 (1995)
[Publications] Mukai, H.: "Identification of pskl^+, encoding a novel putative serine/threonine protein kinase of Schizosaccharomyces pombe, whose mutation conferred resistence to phenylarsine oxide." Gene. 166. 155-159 (1995)
[Publications] Takanaga, H.: "Functional characterization of the promoter region of the mouse protein kinase C γgene." FEBS Lett.368. 276-278 (1995)
[Publications] Mukai, H.: "Xenopus PKN: cloning and sequencing of the cDNA and identification of conserved domains." Biochim. Biophys. Acta. 1261. 296-300 (1995)
[Publications] Hirano, M.: "MEK kinase is involved in TNF α mediated activation of NFκB and degradation of IκBα." J. Biol. Chem.(in press).
[Publications] Akimoto, K.: "EGF and PDGF receptors activate atypical PKCλ through phosphatidylinositol 3-kinase." EMBO J.15. 788-798 (1996)
[Publications] Ueda, E.: "The η isoform of protein kinase C mediates transcriptional activation of the human transglutaminase I gene." J. Biol. Chem.(in press).
[Publications] Hirai, S.: "Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK." Oncogene. 12. 641-650 (1996)
[Publications] Moriya, S.: "PDGF activates protein kinase C ε through redundant and independent signaling pathways involving phosphpholipase C γ or phosphatidylinositol 3-kinase." Proc Natl. Acad. Sci. U. S. A.93. 151-155 (1996)
[Publications] Suzuki, K.: "Two family members of calpain: ubiquitous and tissue specific calpains." Expression of tissue proteinases andregulation of protein degradation as related to meat quality., ECCEAMST, The Netherlands. 5-15 (1995)
[Publications] Nishioka, N.: "Wortmannin inhibits the activation of MAP kinase following Vasopressin V1 receptor stimulation." FEBS Lett.377. 393-398 (1995)
[Publications] Nishioka, N.: "Phosphatidylinositol 3-kinase is involved in TRE-dependent gene expression in response to arginine vasopressin." Biochem. Biophys. Res. Commun.215. 1037-1042 (1995)
[Publications] Morishita, R.: "Primary structure of a γ subunit of G protein, γ10 and its phosphorylation by protein kinase C." J. Biol. Chem.270. 29469-29475 (1995)
[Publications] Ogawara, M.: "Differential Targeting of protein kinase C and CaM kinase II signaling to vimentin." J. Cell Biol.131. 1055-1056 (1995)
[Publications] Wang, F.: "Stimulatory antibody-induced activation and selective translocation of protein kinase C isoenzymes in human platelets." Biochem. J.311. 401-406 (1995)
[Publications] Kinouchi, T.: "Conventional protein kinase C (PKC)-α and novel PKCε, but not-δ, increase the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein from PKC cDNA transfected 3Y1 fibrobrasts." FEBS Lett.364. 203-206 (1995)
[Publications] Ichikawa, S.: "Solution structure of cysteine-rich domain of protein kinase Cα." J. Biochem.117. 566-574 (1995)
[Publications] Yoshinori Asaoka Yosuke Tsujishita Yasutomi Nishizuka: "Lipid signaling for protein kinase C activation In: Handbook of Lipid Research, vol. 8 Lipid second messengers" Robert M. Bell Stephen M. Prescott John H, Exton, 59-74 (1996)
[Publications] Yamamoto, S.: "Molecular Biology of the Arachidonate Cascade" Elsevier(in press),
[Publications] Nakashima, S.: "Handbook of Experimental Pharmacology, ″Platelets and their factors″" Platelet phospholipase C, D. Bruchhausen, V. and Walter, U., eds.)Springer-Verlag,(in press) (1996)
[Publications] Yamamura, H.: "Syk Spleen tyrosine kinase(vertebrates)in The Protein Kinase Factsbook Vol. II." G. Hardie and S. Hanks, Academic Press Limited., 109-111 (1995)
[Publications] Ohno, S.: "YKR2 PK(S. cerevisiae), The protein kinase factbook" Academic Press Limited., 1 (1995)
[Publications] Ohno, S.: "Protein kinase C(vertebrates)Ca^<2+>-& phospholipid-dependent protein kinase, The protein kinase factbook" Academic Press Limited., 9 (1995)
[Publications] 秋山徹: "癌抑制遺伝子の最前線" 横田淳秋山徹, 158 (1995)
[Publications] 秋山徹: "転写のしくみと疾患" 村松正實, 163 (1996)
[Publications] 立花太郎: "GTP結合蛋白質" 羊土社, 312 (1995)
[Publications] N. Sato, S. Iwata, A. Yamauchi, T. Hori, and J. Yodoi.: "Methods in Enzymology, Biothiols." Academic Press, 382 (1995)
[Publications] J. Yodoi and T. Uchiyama.: "Adult T cell Leukemia and Related Diseases" R. G. Landes Company, 139 (1995)
[Publications] T. Masaki: "Annual Review of Pharmacology and Toxicology" Annual Reviews Inc., 21 (1995)
[Publications] T. Masaki: "Endothelin: Role in Health and Disease" Harwood Academic Publishers gmbh, 11 (1995)

1995 Fiscal Year Annual Research Report

細胞内情報伝達機構網の研究

Principal Investigator

西塚 泰美 神戸大学, 学長 (10025546)

Research Products

[Publications] Inoue, H.: "Potential role of protein phosphorylation in GTP-γ-Sdependent activation of phospholipase D." Biochem. Biophys. Res. Commun.210. 542-548 (1995)

[Publications] Yamaguchi, K.: "The protein kinase C isoforms leading to MAP-kinase activation in CHO cells." Biochem. Biophys. Res. Commun.210. 639-647 (1995)

[Publications] Nakamura, S.: "Mammalian phospholipase D: Activation by ammonium sulfate and nucleotides." Proc. Natl. Acad. Sci. USA. 92. 12319-12322 (1995)

[Publications] Nakamura, S.: "Mammalian phospholipase D: Phosphatidylethanolamine as an essential component." Proc. Natl. Acad. Sci. USA. (in press).

[Publications] Sato, K-I.: "Site-specific association of c-Src with epidermal growth factor receptor in A431 cells." Biochem. Biophys. Res. Commun.210. 844-851 (1995)

[Publications] Sato, K-I.: "c-Src phosphorylates epidermal growth factor receptor on tyrosine-845." Biochem. Biophys. Res. Commun.215. 1078-1087 (1995)

[Publications] Sahara, S.: "Biochemical evidence for the interaction of regulatory subunit of cAMP-dependent protein kenase with IDA(Inter-DFG-APE)region of catalytic subunit." FEBS Lett.(in press). (1996)

[Publications] Sato, K-I.: "Purification and characterization of a Src-related p57 protein-tyrosine kinase from Xenopus oocytes: Isolation of an inactive form of the enzyme, and its activation and traslocation upon fertilization." J. Biol. Chem.(in press). (1996)

[Publications] Deng-Shun Wang: "Binding of pleckstrin homology domains to WD40/β-transducin repeat containing segments of the protein product of the Lis-1 gene" Biochem. Biophys. Res. Communi.209. 622-629 (1995)

[Publications] Kakutani Yokoyama: "Phospholipid degradation in rat calcium ionophore-activated platelets is catalyzed mainly by two discrete secretory phospholipase As" J. Biochem.117. 1280-1287 (1995)

[Publications] Kenji Hattori: "Purification and characterization of platelet-activating factor acetylhydrolase II from bovine liver cytosol" J. Biol. Chem.270. 22308-22313 (1995)

[Publications] Hideki Adachi: "cDNA cloning of human cytosolic platelet-activating factor acetylhydrolase g-subunit and its mRNA expression in human tissues" Biochem. Biophys. Res. Communi.214. 180-187 (1995)

[Publications] Mitsuharu Hattori: "Cloning and expression of a cDNA encoding the b-subunit(30-kDa subunit)of bovine brain platelet-activating factor acetylhydrolase" J. Biol. Chem.270. 31345-31352 (1995)

[Publications] Yamamoto, K.: "Transcriptional roles of nuclear factor κB and nuclear factor-interleukin-6 in the tumor necrosis factor α-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells" J. Biol. Chem.(in press).

[Publications] Endo, T.: "Induction of cyclooxygenase-2 is responsible for interleukin-1β-dependent prostaglandin E2 synthesis by human lung fibroblasts" Am. J. Respir. Cell Mol. Biol.12. 358-365 (1995)

[Publications] Ohtsuki, T.: "Reperfusion induces 5-lipoxygenase translocation and leukotriene C_4 production in ischemic brain" Am. J. Physiol.268. H1249-1257 (1995)

[Publications] Nakamura, M.: "Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase in mouse blood cells" J. Histochem. Cytochem.43. 237-244 (1995)

[Publications] Arakawa, T.: "The transcriptional regulation of human arachidonate 12-lipoxygenase gene by NFkB/Rel" FEBS Lett.363. 105-110 (1995)

[Publications] Ueda, N.: "Oxygenation of arachidonylethanolamide(anadamide)by lipoxygenases" Advances in Prostaglandin, Thromboxane, and Leukotriene Research. 23. 163-165 (1995)

[Publications] Katori, M.: "Induction of prostaglandin H synthase-2 in rat carrageenin-induced pleurisy and effect of a selective COX-2 inhibitor" Advances in Prostaglandin, Thromboxane, and Leukotriene Research. 23. 345-347 (1995)

[Publications] Alam, S: "Defective phospholipase D activation in Ki-ras-tansformed NIH3T3 cells: Evidence for downstream effect of PLC-γ1" Biochem. Biophys. Res. Commun.207. 460-466 (1995)

[Publications] Banno, Y.: "Endogenous cleavage of phospholipase Cβ3 by agonist-induced activation of calpain in human platelets" J. Biol. Chem.270. 4318-4323 (1995)

[Publications] Nakamura, Y.: "Effects of an anti allergic drug, permirolast potassium on tyrosine phosphorylation and MAP kinase activation in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells" Jpn. J. Allergol.44. 34-44 (1995)

[Publications] Nagata, K.: "Possible interaction of hemoglobin with a low Mr GTP-binding protein ram p25" Biochem. Mol. Biol. Int.35. 507-515 (1995)

[Publications] Fujita, H.: "Functions of mutant gelsolin, His 321 isolated from a flat revertant of Ras-transformed cells" Eur. J. Biochem.229. 615-620 (1995)

[Publications] Nagata, K.: "A low molecular GTP-binding protein, Rap1, in human platelets: Locali-zation, translocation and phosphorylation by cyclic AMP-dependent protein kinase" Brit. J. Haematol.90. 180-186 (1995)

[Publications] Ohguchi, K.: "Activation of membrane-bound phospholipase D by protein kinase C in HL-60 cells: Synergistic action of a small GTP-binding protein RhoA" Biochem. Biophys. Res. Commun.211. 306-311 (1995)

[Publications] Nakashima, S.: "Delection and site-directed mutagenesis of EF-hand domain of phospholipase C-delta 1: Effects on its activity" Biochem. Biophys. Res. Commun.211. 364-369 (1995)

[Publications] Adachi, T.: "Roles of prostaglandin production and MAP kinase activation in hepatocyte growth factor-meiated rat hepatocyte proliferation" Hepatology. 21. 1668-1874 (1995)

[Publications] Kumada, T.: "Antigen-mediated phospholipase D activation in rat basophilic leukemia(RBL-2H3)cells: Involvement of calcium/calmodulin" Biochim. Biophys. Acta. 1258. 107-114 (1995)

[Publications] Liu, B.: "Implication of protein kinase Cα in PAF-stimulated phospholipase D(PLD)activation in Chinese hamster ovary(CHO)cells expressing PAF receptor" Biochem. Biophys. Res. Commun.214. 418-423 (1995)

[Publications] Nagata, K.: "Identification of heterotrimeric GTP-binding proteins in human megakaryoblastic leukemia cell, MEG-O1, and their alteration during cellular differentiation" Life Sci.57. 1675-1681 (1995)

[Publications] Nakamura, Y.: "C2-ceramide inhibits IgG-mediated phospholipase D but not C activation in rat basophilic leukemia(RBL-2H3)cells" J. Immunol.156. 256-262 (1996)

[Publications] Ohguchi, K.: "Regulation of membrane-bound phospholipase D by protein kinase C in HL-60 cells: Synergistic action of small GTP-binding protein RhoA" J. Biol. Chem.271. 4366-4373 (1996)

[Publications] Nagata, K.: "Identification and localization of gene expression of a low Mr GTP-binding protein, Ram p25 in pituitary gland" Biochem. Biophys. Res. Commun.217. 1223-1230 (1996)

[Publications] Adachi, T.: "Mitogen-activated protein kinase activation in hepatocyte growth factor-stimulated rat hepatocytes: Involvement of protein tyrosine kinase and protein kenase C" Hepatology. (in press).

[Publications] Kentarou Hanada: "Both Sphingolipids and Cholesterol Participate in the Detergent Insolubility of Alkaline Phosphatase, a Glycosylphosphatidylinositol-anchored Protein, in Mammalian Membranes" J. Biol. Chem.270. 6254-6260 (1995)

[Publications] Masao Shiozaki: "Syntheses of 1-0-[5-(Carboxy)pentanoyl]-2-deoxy-2-(2,2-dif-luorotetradecanamido)-3-0-[(R)-3-(tetradecanoyloxy)tetradecanoyl]-4-0-phosphono-α-D-gllucopyranose and Its Analogues" Biosci. Biotech. Biochem.59. 501-506 (1995)

[Publications] Jinhua Xu: "Identification of a Hemocyte Membrane Protein of the Silkworm, Boabyx mori, Which Specifically Binds to Bacterial Lipopoly-saccharide" Insect Biochem. Molec. Biol.25. 921-928 (1995)

[Publications] Igarashi, K.: "A novel phosphatidylserine-binding peptide motif defined by an anti-idiotypic momoclonal antibody: Localization of phosphatidylserine-specific binding sites on protein kinase C and phosphatidylserine decarboxylase." J. Biol. Chem.270. 29075-29078 (1995)

[Publications] Igarashi, K.: "Specific binding of a synthetic peptide derived from an antibody complementarity determining region to phosphatidylserine." J. Biochem.117. 452-457 (1995)

[Publications] Tokita, S.: "Specific cross-reaction of IgG anti-phospholipid antibody with platelet glycoprotein IIIa." Thromb. Haemost.75. 168-174 (1996)

[Publications] Nagai, K. et al.: "Tyrosine phosphorylation of Shc is mediated through Lyn and Syk in B cell receptor signaling." J. Biol. Chem.270(12). 6824-6829 (1995)

[Publications] Yanagi, S. et al.: "The structure and function of p72^<syk> expressed in hematopoietic cells21GC01:Cellular Signalling" 7(3). 185-193 (1995)

[Publications] Qin, S. et al.: "Activation and tyrosine phosphorylation of p72^<syk> as well as calcium mobilization after hydrogen peroxide stimulation in peripheral blood lymphocytes." Biochem. J.308(1). 347-352 (1995)

[Publications] Hirasawa, N.: "A requirement for syk in the activation of the microtubule-associated protein kinase/phospholipase A2 pathway by FceRl is not shared by a G protein-coupled receptor." J. Biol. Chem.270. 10960-10967 (1995)

[Publications] Ozaki, Y.: "Anti-CD9 monoclonal antibody activates p72syk in human platelets" J. Biol. Chem.270. 15119-15124 (1995)

[Publications] Maeda, H.: "Possible involvement of protein-tyrosine kinases such as p72syk in the Disc-Sphere change response of porcine platelets." J. Biochem.117. 1201-1208 (1995)

[Publications] Yang, C.: "Syk and Lyn are involved in radiation-induced signaling, but inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis." J. Biochem.118. 33-38 (1995)

[Publications] Asahi, M.: "Cyclic AMP-elevating agents negatively regulate the activation of p72syk in N-formyl-methionyl-leucyl-phenylalanine receptor signaling." Biophys. Biochem. Res. Commun.212. 887-893 (1995)

[Publications] Scharenberg, A. M.: "Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering." EMBO J.14. 3385-3394 (1995)

[Publications] Hashimoto, E.: "Purification and phosphorylation of Mr 25,000 protein, an effective phosphate acceptor for casein kinase II and protein kinase C, detected in the cytosolic fraction of Xenopus laevus oocytes." J. Biol. Chem.118. 453-460 (1995)

[Publications] Ichinohe, T.: "Cyclic AMP-insensitive activation of c-Src and Syk protein-tyrosine kinases through platelet membrane glycoprotein VI." J. Biochem.270. 28029-28036 (1995)

[Publications] Zeng, H.: "Phosphorylation of HSl, GAP-associated p190 and a novel GAP-associated p60 protein by cross-linking of FcgRIIIA." J. Biochem.118. 1166-1174 (1995)

[Publications] Kurosaki, T.: "Syk recruitment to Ig-a and its phosphorylation are essential for B cell antigen receptor signaling." J. Exp. Med.(in press). (1996)

[Publications] S. Shimihama, G. Perry, P. Richey, D. Praprotnik, T. Takenawa, K. Fukami, P. J. Whitehouse, J. Kimura: "Characterization of the association of phospholipase C-d with Alzheimer neurofibrillary tangles" Brain Research. 669. 217-224 (1995)

[Publications] J. C. Hay, P. L. Fisette, G. H. Jenkins, K. Fukami, T. Takenawa, R. A. Anderson and T. F. J. Martin: "ATP-dependent inositide phosphorylation required for Ca2+-activated secretion" Nature. 374. 173-177 (1995)

[Publications] H. Hosoya, K. Shimazaki, S. Kobayashi, H. Takahashi, T. Shirosawa, T. Takenawa and K. Watanabe: "Developmental expression of the neural adhesion molecule F3 in the rat brain" Neuroscience Lett.186. 83-86 (1995)

[Publications] Dusko, I.: "Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice" Nature. 377. 539-544 (1995)

[Publications] Tokai, N.: "Kid, a novel kinesin-like DNA binding protein, is colocalized with the chromosomes during mitosis" EMBO J.(in press).

[Publications] Nishizumi, H.: "Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice" Immunity. 3. 549-560 (1995)

[Publications] Kuramochi, S.: "Molecular cloning and characterization of Byp, a murine receptor-type tyrosine phosphatase similar to human DEP-1" FEBS Letters. (in press).

[Publications] Kuroda, S.: "Purification and characterization of REKS from Xenopus eggs-Identification of REKS as a Ras-dependent mitogen-activated kinase kinase kinase." J. Biol. Chem.270. 2460-2465 (1995)

[Publications] Yamamoto, T.: "A novel GTPase-activating protein for R-ras, R-Ras GAP." J. Biol. Chem.270. 30557-30561 (1995)

[Publications] Gotoh, T.: "Identification of Rapl as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G." Mol. Cell. Biol.15. 6746-6753 (1995)

[Publications] Miyazaki, M.: "Rabphilin-3A binds to a Mr 115,000 polypeptide in phosphatidylserine-and Ca^<2+> dependent manner." Mol. Brain Res.28. 29-36 (1995)

[Publications] Amano, K.: "Identification of a putative target for Rho as a serine-threonine kinase protein kinase N." Science. 271. 648-651 (1996)

[Publications] Kuriyama, M.: "Identification of AF-6 and Canoe as putative targets for Ras." J. Biol. Chem.271. 607-610 (1996)

[Publications] Matsui, T.: "Rho-associated kinase, a novel serine/threonine kinase, as a putative target for the small GTP-binding protein Rho." EMBO J.(in press).

[Publications] Kumagai, N., et al.: "Lysophosphatidic acid-induced activation of protein ser/thr kinases in cultured rat 3Yl fibroblasts: possible involvement in rho p21-mediated signalling." FEBS Letters.366. 11-16 (1995)

[Publications] Seckl, M. J., et al.: "Guanosine 5′-3-O-(thio)triphosphate stimulates tyrosine phosphorylation of p125^<FAK> and paxillin in permeabilized Swiss 3T3 cells." Journal of Biological Chemistry.270. 6984-6990 (1995)

[Publications] Madaule, P., et al.: "A novel partner for the GTP-bound forms of rho and rac." FEBS Letters.377. 243-248 (1995)

[Publications] Watanabe, G., et al.: "Protein kinase N(PKN)and PKN-related protein rhophilin as targets of small GTPase Rho." Science. 271. 645-648 (1996)

[Publications] Ishizaki, T., et al.: "The small GTP-binding protein Rho binds to and activates a 160kDA Ser/Thr protein kinase homologous to myotonic dystrophy kinase." EMBO. J.(in press).

[Publications] Reid, T., et al.: "Rhotekin, a new Rho target protein bearing homology to a serine threonine kinase, PKN, and rhophilin in the Rho binding domain." J. Biol. Chem.(in press).

西塚泰美神戸大学, 学長 (10025546)

[Publications] 秋山徹: "癌抑制遺伝子の最前線" 横田淳秋山徹, 158 (1995)

[Publications] 秋山徹: "転写のしくみと疾患" 村松正實, 163 (1996)

[Publications] 立花太郎: "GTP結合蛋白質" 羊土社, 312 (1995)