1996 年度実績報告書

細胞内情報伝達機構網の研究

研究課題

研究課題/領域番号	08NP0601
研究機関	神戸大学
研究代表者	西塚泰美神戸大学, 学長 (10025546)
研究分担者	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, 大学院・農学生命科学研究科, 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)
キーワード	ホスホリパーゼA / 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 / ストレス / ホスファチジルイノシトール3キナーゼ / 核局在化シグナル
研究概要	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研究班を組織した。総括班は研究計画の統合推進を担当し、全体会議および国際シンポジウムの開催により研究者間の円滑な交流をはかるとともに中枢神経におけるプロテインキナーゼC(PKC)の役割や植物の情報伝達機構の研究組織を強化することを検討した。6研究班は以下の成果を収めた。 1.研究班1:情報伝達に関するリン脂質分解酵素として新たに、酸化リン脂質選択的ホスホリパーゼA2(PAF-AHイソフォームII型)、ホスファチジルセリン特異的ホスホリパーゼA1のクローニングを行い、また発生過程の脳に特異的に発現するPAF分解酵素(PAF-AHイソフォームI型)の高次構造が三量体G蛋白質と酷似していることを示した。ラットのホスホリパーゼD1,D2遺伝子のクローニングをほぼ完成し,HL-60細胞における膜結合性ホスホリパーゼDがRho、ARFとPKCによって相乗的に活性化される発見し、また、CD14を介するLPS刺激伝達にホスホリパーゼDが関与すること、およびクルクミンがホスホリパーゼD活性を阻害する事を見い出した。膜リン脂質、特にホスファチジルエタノールアミンの動態がアクチンフィラメントの再構築に関わることを発見した。情報伝達の末端にあるサイクロオキシゲナーゼの分化に伴う発現誘導を血小板前駆細胞について検討した。 2.研究班2:非受容体型チロシンキナーゼSykが活性酸素によって強く活性化され、過酸化水素による細胞内カルシウム増加やJNKの活性化などの生理的応答はSykに依存することを明らかにした。核内にホスホリパーゼCδが存在することを見い出し、また、核内ではホスホリパーゼCの基質であるホスファチジルイノシトール4、5二リン酸(PIP2)がヒストンに結合しており、PIP2の結合はヒストンによる転写阻害を抑制し、ヒストンがPKCによりリン酸化を受けることによりPIP2とヒストンの結合が減少することから、核内にもイノシトールリン脂質情報伝達系が存在し転写制御に関与していることが示唆された。記憶などに関与するNMDA受容体はそのチャネル活性がチロシン燐酸化により制御されることが知られているが、NMDA受容体とFynの共発現系培養細胞とFyn欠損マウスの脳抽出液を用い、FynチロシンキナーゼがNMDA受容体のチロシンリン酸化を引き起こすことを … もっと見る強く示唆する結果を得た。低分子量G蛋白質Rhoの標的としてPKN、Rhoキナーゼ、ミオシンホスファターゼのミオシン結合サブユニット(MBS)を見い出し、Rhoキナーゼがミオシンを直接リン酸化すると共にMBSをリン酸化してホスファターゼの活性を抑制すること、およびRhoキナーゼがRhoの下流でアクチンストレスファイバーの形成と接着斑の形成を制御することを明らかにした。 3.研究班3:ホスファチジルイノシトール3-キナーゼ(PI3キナーゼ)の下流の標的として細胞増殖因子により活性化されることが知られているRACプロテインキナーゼが、PI3キナーゼを介さずに熱ショックや高浸透圧といったストレスにより活性化を受けることを見い出した。PI3キナーゼ経路の代表的な下流因子、p70S6キナーゼの活性化機構にaPKCλが関与していることを明らかにし、また、aPKCλ結合蛋白質としてPDZドメインを有する新規蛋白質を見い出し、この結合蛋白質が線虫の卵不等分裂に関わる遺伝子のほ乳類ホモログであることを示した。PKNが中間径フィラメントであるニューロフィラメント、ビメンチンおよびαアクチニンと直接結合し、PKNはリン酸化により中間径フィラメントの重合、脱重合を制御していることを示した。また、PKNが熱などのストレスにより速やかに核に移行することを見い出し、PKNが遺伝子発現制御を含む核内機能に関与することが示唆された。大腸癌の癌抑制遺伝子APCの産物がショウジョウバエ癌抑制遺伝子DLGのヒトホモログ産物と複合体を形成していることを見い出し、これらの癌抑制遺伝子産物のリン酸化の検討により、DLG蛋白質はG2期からM期にかけてリン酸化が増大し、このリン酸化にはCDC2が関与していることが示唆された。 4.研究班4:細胞の分化増殖に関わる情報伝達と転写因子の核移行について検討し、以下の成果を得た。PKCη分子種によるケラチノサイト分化についてトランスジェニックマウスを用いて検討し、皮膚、食道、角膜など扁平上皮に分化の異常を見い出し、η分子種の中心的役割を確認した。へパリン結合性EGF様増殖因子のジャックスタクリン活性とパラクリン活性をラット肝癌細胞株を用いて比較検討し、ジャクスタクリン活性はサバイバル因子として機能することを示した。また、活性型P13キナーゼを細胞に発現させることによりP13キナーゼの細胞骨格の組織化、小包輸送への関与を示唆した。転写因子JunとFosの核輸送を調べ、両者は二量体としてJunの核局在配列を利用して核輸送されることを明らかにし、核局在配列の強弱の組合わせが遺伝子発現に関与することを示唆し、また、インターフェロンγの刺激に依存したStat1分子の核内移行を解析し、低分子量G蛋白質Ran、核膜孔ターゲティング複合体構成因子であるimportinが必要であることを明らかにした。 5.研究班5:微小管形成に関わるplk分子がM期開始よりリン酸化を受け、細胞分裂の調節に関わっていることを示し、GO期が維持できるプロB細胞でのみ発現が見られる遺伝子のクローニングを進行している。抗Fasモノクローナル抗体で刺激後活性化される34kDのプロテインキナーゼを見い出し、さらにこのプロテインキナーゼと共精製されるチオレドキシン(TRX)様構造を持つ蛋白質を見い出した。TRX会合蛋白質の同定に成功し、TRXの核移行、還元物質REF-1との直接結合を明らかにし、TRXノックアウトマウスの解析を進め、TRX遺伝子の発現が胚の初期分化に必須であることを証明した。さらに、転写因子PEBP2/AML1のDNA結合能がレドックス制御下にあることを示した。前年度までに樹立したNKT細胞を用いて、これらを特異的に認識するモノクローナル抗体を作製し、自己免疫疾患モデルマウス、妊娠マウスでのNKT細胞の役割の解析を進めた。 6.研究班6:ウシ大動脈内皮型-酸化窒素合成酵素(beNOS)のcDNAをエンドセリン-1プロモーター下流に組み込み、beNOS過剰発現トランスジェニックマウスの作成を行ない、beNOSのmRNAおよび蛋白質が大動脈をはじめ、心、肺等の主要臓器の血管内皮細胞に発現されていることを認めた。肺動脈平滑筋において、エンドセリン-1などによる[Ca2+]i非依存性収縮は持続性であり、PKC阻害薬で抑制されるがMLCK阻害薬では抑制されないことを示し、また血管平滑筋にはCa2+感受性に関与するRho associated kinaseが発現することを明らかにした。ウシ大動脈内皮細胞においてリゾPCにより130kD、190kDの蛋白質がチロシンリン酸化され、この130kDはRECAM-1であることことが判明した。またリゾPCにより内皮細胞膜表面のRECAM-1がチロシンリン酸化されることが明かになった。分裂酵母系を用いて、PP2Bと機能的に関連した新たなMAPキナーゼホモログであるPmk1を発見した。また、PP2Bが長期増強現象や血球系の分化に関与していることを明かにした。隠す

研究成果

(115件)

すべてその他

すべて文献書誌 (115件)

[文献書誌] Nakamura,S.: "Mammalian phospholipase D : Phosphatidylethanolamine as an essential component." Proc.Natl.Acad.Sci.USA. 93. 4300-4304 (1996)
[文献書誌] Shimooku,K.: "Reconstitution of GTP-γ-S-dependent phospholipase D activity with ARF,RhoA,and a soluble 36-kDa protein." FEBS Lett.387. 141-144 (1996)
[文献書誌] Nakamura,S.: "Phoshatidylcholine hydrolysis and protein kinase Cactivation for intracellular signaling network." J.Lipid Mediators Cell Signalling. 14. 197-202 (1996)
[文献書誌] 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 translocation upon fertilization." J.Biol.Chem.271. 13250-13257 (1996)
[文献書誌] Tokmakov,A.: "Phosphoregulatory tyrosine of Xenopus MAP kinase is out of the reach of the enzyme's catalytic center after autophosporylation. Biochemical evidence for conformational changes upon phosphorylation." Eur.J.Biochem.241. 322-329 (1996)
[文献書誌] Fukami,Y.: "Activation and translocation of a Src-family protein tyrosine kinase in fertilized Xenopus eggs." J.Reprod. & Develop.43 (in press). (1997)
[文献書誌] Fukasawa,M.: "SRB1,a class B scavenger receptor,recognizes both negatively charged liposomes and apoptotic cells." Exp.Cell Res.222. 246-250 (1996)
[文献書誌] Tokita,S.: "Specific cross-reaction of IgG anti-phospholipid antibody with platelet glycoprotein IIIa." Thromb.Haemost.75. 168-174 (1996)
[文献書誌] Hara,N.: "Lysophosphatidylserine enhances exogenous type II phospholipase A2-induced activation of rat serosal mast cells." Biol.Pharm.Bull.19. 474-476 (1996)
[文献書誌] Kim,H.S.: "Age-related changes of a-tocopherol transfer protein expression in rat liver." J.Nutr.Sci.Vitaminol.42. 11-18 (1996)
[文献書誌] Emoto,K.: "Redistribution of phosphatidylethanolamine at the cleavage furrow of dividing cells during cytokinesis." Proc.Natl.Acad.Sci.USA. 93. 12867-12872 (1996)
[文献書誌] Matsuzawa,A.: "Release of secretory phospholipase A2 from rat neuronal cells and its possible function in the regulation of catecholamine secretion." Biochem.J.318. 701-709 (1996)
[文献書誌] Lan,F.: "Extended fitness of variable region primers by a novel PCR protocol." J.Immunol.Methods. 195. 27-32 (1996)
[文献書誌] Hattori,K.: "cDNA cloning and expression of intracellelar platelet-activating factor (PAF) acetylhydrolase II." J.Biol.Chem.271. 33032-33038 (1996)
[文献書誌] Hattori,M.: "PAF and PAF acetylhydrolase in the nervous system." J.Lipid Mediators Cell Signalling. 14. 99-102 (1996)
[文献書誌] Albrecht,U.: "Platelet-activating factor acetylhydrolase expression and activity suggest a link between neuroral migration and platelet-activating factor." Devel.Biol.180. 579-593 (1996)
[文献書誌] Kudo,I.: "Function of type II phospholipase A2 in dopamine secretion by rat neuronal PC12 cells." J.Lipid Mediators Cell Signalling. 14. 25-31 (1996)
[文献書誌] Ho,Y.S.: "Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer." Nature. 385. 89-93 (1996)
[文献書誌] Sato,T.: "Serine Phospholipid-specific phospholipase A that is secreted from activated platelets" J.Biol.Chem.272. 2192-2198 (1997)
[文献書誌] Ueda,N.: "Induction of cyclooxygenase-1 in a human megakaryoblastic cell line (CMK) differentiated by phorbol ester." Biochim.Biophys.Acta.1344. 103-110 (1997)
[文献書誌] Harada,Y.: "Role of prostaglandin H synthase-2 in prostaglandin E2 formation in rat carrageenininduced pleurisy." Prostaglandins. 51. 19-33 (1996)
[文献書誌] Ikawa,H.: "Arachidonate 12-lipoxygenase in porcine anterior pituitary cells : its localization and possible function in gonadotrophs." J.Endocrinol.148. 33-41 (1996)
[文献書誌] Nakamura,M.: "Subcellular localization of arachidonate 12-lipoxygenase and morphological effect of its overexpression on murine kerationcyes." Cell Tissue Res.(in press). (1997)
[文献書誌] Nishioka,N.: "Gene of rat Ca^<2+>/calmodulin-dependent protein kinase IIα isoform cloning and whole structure." FEBS LEtt.396. 333-336 (1996)
[文献書誌] Ueda,N.: "Enzymes for anandamide biosynthesis and metabolism." J.Lipid Mediators Cell Signalling. 14. 57-61 (1996)
[文献書誌] Nakamura,Y.: "C2-ceramide inhibits IgG-mediated phospholipase D but not C activation in rat basophilic leukemia (RBL-2H3) cells." J.Immunal.156. 256-262 (1996)
[文献書誌] Ohguchi,K.: "Regulation of membranebound phospholipase D by protein kinase C in HL-60 cells : Synergistic of small GTP-binding protein RhoA." J.Biol.Chem.271. 4366-4373 (1996)
[文献書誌] Nakashima,S.: "Molecular cloning of Δ9 fatty acid desaturase from protozoan Tetrahymena thermophila and its mRNA expression during thermal membrane adaptation." Biochem.J.317. 29-34 (1996)
[文献書誌] Liu,B.: "PLD activation in Chinese hamster ovary (CHO) cells transfected with PGF2 αreceptor cDNA." Prostaglandins. 51. 233-248 (1996)
[文献書誌] Adachi,T.: "Mitogenactivated protein kinase activation in hepatocyte growth factor-stimulated rat hepatocytes : Involvement of protein tyrosine kinase and protein kinase C." Hepatology. 23. 1244-1253 (1996)
[文献書誌] Kovacs,P.: "Phospholipase D activity in the Tetrahymena pyriformis." Biochem.Biophys.Res.Commun.222. 359-361 (1996)
[文献書誌] Banno,Y.: "Differential translocation of phospholipase C isozymes to integrin-mediated cytoskeletal complexes in thrombin^stimulated human platelets." J.Biol.Chem.271. 14989-14994 (1996)
[文献書誌] Kumada,T.: "Phenylarsine oxide (PAO)-mediated activation of phospholipase D in rat basophilic leukemia (RBL-2H3) cells : Possible involvement of calcium and protein kinase C." Immunobiology. 195. 347-359 (1996)
[文献書誌] Sakai,H.: "Suppressed expression of CD44 variant isoforms during human glioma A172 cell differentiation induced by cyclic AMP." Neurosci.Lett.210. 189-192 (1996)
[文献書誌] Nagata,K.: "Protein Kinase C isozymes in human megakaryoblastic leukemia cell line,MEG-01 : Possible involvement ot the isozymes in the differentiation process of MEG-01 cells." Br.J.Haematol.93. 762-771 (1996)
[文献書誌] Ojio,K.: "Effect of Clostridium difficile toxin B on IgE receptor-mediated signal transduction in rat basophilic leukemia cells : inhibition of phospholipase D activation." Biochem.Biophys.Res.Commun.224. 591-596 (1996)
[文献書誌] Alam,S.: "Molecular cloning a gene encoding acid α-glucosidase from Tetrahymena pyriformis." J.Eukaryot.Microbiol.43. 295-303 (1996)
[文献書誌] Nakamura,Y.: "Brefeldin A inhibits antigen-or calcium ionophore-stimulated but not PMA-induced phospholipase D activation in raty basophilic leukemia (RBL-2H3) cells." Immunobiology. 195. 231-242 (1996)
[文献書誌] Yoshimura,S.: "Differential mRNA expression of phospholipase D (PLD) isozymes during cAMP-induced differentiatiion in C6 glioma cells." Biochem.Biophys.Res.Commun.225. 494-499 (1996)
[文献書誌] Banno,Y.: "Membrane-associated phospholipase D activity in neural cell line PC12." J.Lipid Mediators Cell Signaling. 14. 237-243 (1996)
[文献書誌] Mirbod,F.: "Molecular cloning of a gene encod translation initiatiion factor (TIF) from C.albicans." J.Med.Vet.Mycol.34. 393-400 (1996)
[文献書誌] Ohguchi,K.: "Effect of Clostridium difficile Toxin A and Toxin B on Phospholipase D activation in human promyelocytic leukemic HL60 cells." Infect.Immun.64. 4433-4437 (1996)
[文献書誌] Hashii,M.: "Bradykinin-activated two signal pathways of protein tyrosine phosphorylation and formation of inositol tetrakisphosphates merge at the Ca^<2+> influx process in ras-transformed NIH3T3 fibroblast cells." Biochem.J.319. 649-656 (1996)
[文献書誌] Adachi,T.: "Phospholipase D activation in hepatocyte growth factor-stimulated rat hepatocytes ; Implication in the expressions of c-jun and c-fos." Hepatology. 24. 1274-1281 (1996)
[文献書誌] Shirato,L.: "Down regulation of protein kinase C during growth enhancement induced by interleukin-6 on a human myeloma cell line,KMS-11." Cancer Lett.107. 131-136 (1996)
[文献書誌] Zhao,Y.: "Molecular cloning of dalta 9 fatty acid desaturase and growth associated chages in its mRNA expression in Tetrahymena pyriformis" Eur.J.Protistol.32. 539-544 (1996)
[文献書誌] Ohguchi,K.: "Enhancement of phospholipase D activity during differentiation in human promyelocytic leukemic HL60 cells : involvement of RhoA translocation to membranes." J.Biol.Chem.272. 1990-1996 (1997)
[文献書誌] Ito,Y.: "Impllcation of Ca^<2+>-dependent protein tyrosinephosphorylation in carbachol-induced phospholipase D activation in rat pheochromocytoma PC12 cells." J.Neurochem.68. 419-425 (1997)
[文献書誌] Hammond,S.M.: "Characterization of two alternately spliced forms of phospholipase D1." J.Biol.Chem.(in press). (1997)
[文献書誌] Nakashima,S.: "Differential expression of protein kinase C isozymes and small GTP-binding proteins during HL-60 cells differentiation by retinoic acid and cyclic AMP : Relation with phospholipase D (PLD) activation." Immunobiology. (in press). (1997)
[文献書誌] Yoshimura,S.: "Differential expression of rho family GTP-binding proteins and protein kinase C isozymes during C6 glial cell differentiation." Mol.Brain Res.(in press). (1997)
[文献書誌] Tekemura,O.S.: "Inhibition of fMLP-stimulated tyrosine phosphorylation and PLD activation by quercetin in rabbit neutrophils." Biochem.Pharmacol.(in press). (1997)
[文献書誌] Nagata,K.: "Differential expression of low Mr GTP-binding proteins in human megakaryoblastic leukemia cells,MEG-01,and their possible involvement in the differentiatiion process." Thromb.Haemost.(in press). (1997)
[文献書誌] Banno,Y.: "Nuclear ADP-ribosylation factor (ARF)-and oleate-dependent phospholipase D in rat liver cells : Increases of ARF-dependent PLD activity in regenerating liver cells." J.Biol.Chem.(in press). (1997)
[文献書誌] Mirbod,F.: "Molecular cloning of a Rho family,CDC42α gene from Candida albicans and its mRNA expression Changes during morphogenesis." J.Med.Ved.Mycol.(in press). (1997)
[文献書誌] Shiozaki,M.: "Stereocontrolled Synthesis of All Stereoisomers of the Proposed Flavolipin" Tetrahedron Lett.37. 3875-3876 (1996)
[文献書誌] Shiozaki,M.: "Synthesis of GLA-60 Positional Isomer as an LPS-Agonist and Its Activity" Chem.Lett.735-736 (1996)
[文献書誌] Saito,K.: "Immunochemical identification of the pssA gene product as phosphatidylserine synthase I of Chinese hamster ovary cells" FEBS Lett.395. 262-266 (1996)
[文献書誌] Karasawa,K.: "Cloning,Expression and Characterization of Plasma Platelet-Activating Factor-Acetylhydrolase from Guinea Pig" J.Biochem.120. 838-844 (1996)
[文献書誌] Kuge,O.: "Post-translational processing of the phosphatidylserinedecarboxylase gene product in Chinese hamster ovary cells" Biochem.J.319. 33-38 (1996)
[文献書誌] Fukasawa,M.: "Involvement of Heparan Sulfate Proteoglycans in the Bioding step for phagocytosis of Latex Beads by Chinese Hamster Ovary Cells" Exp.Cell Res.230. 154-162 (1997)
[文献書誌] Muro,M.: "Role of CD14 Molecules in Internalization of Actinobacillus actinomycetemcomitans by Macrophages and Subsequent Induction of Apoptosis" Infect.Immun.in press. (1997)
[文献書誌] Fujimoto,K.: "Transmembrane phospholipid distribution revealed by freeze-fracture replica labeling." J.Cell Sci.109. 2453-2460
[文献書誌] Shiratsuchi,A.: "Recognition of phosphatidylserine on the surface of apoptic spermatogenic cells and subsequent phagocytosis by Sertoli cells of the rat." J.Biol.Chem.272. 2354-2358 (1997)
[文献書誌] Emoto,K.: "Exposure of Phosphatidylethanolamine on the surface of apoptotic cells." Exp.Cell Res.232. in press (1997)
[文献書誌] Hashimoto,E.: "Phosphorylated Sites of Mr 25,000 Protein,a Putative Protein Phosphatase 2A Modulator,and Phosphorylation of the Synthetic Peptide Containing These Sites by Protein Kinase C." J.Biochem.119. 626-632 (1996)
[文献書誌] Qin,S.: "Cooperation of tyrosinekinases p72 syk and p53/56 lyn regulates calcium mobilization in chicken B cell oxidant strss signaling." Eur.J.Biochem.236. 443-449 (1996)
[文献書誌] Minami,Y.: "Role of protein-tyrosine kinases in stress signaling." J.Deuterium Sci.5. 11-14 (1996)
[文献書誌] Nakamura,T.: "Sigunal transduction through mk B-cell receptors on mature B cells." Immunology. 88. 593-599 (1996)
[文献書誌] Yanagi,S.: "CD45 Nodukates phosphorylation of Both Autophosphorylation and Negative Regulatory Tyrosines of Lyn in B Cells." J.Biol.Chem.271. 30487-30492 (1996)
[文献書誌] Wang,X.: "Tyrosine Phosphrylation and Syk Activation Are Involved in Thrombin-Induced Aggregation of Epinephrine-Potentiated Platelets." J.Biochem.121. 325-330 (1997)
[文献書誌] Qin,S.: "Syk-dependent and-independent Signaling Cascades in B Cells Elicited by Osmotic and Oxidative Stress." J.Biol.Chem.(in press). (1997)
[文献書誌] Liu,N.: "A new phospholipase C d4 is induced at S-phase of cell cycle and appears in nucleus" J.Biol.Chem.271. 355-360 (1996)
[文献書誌] Fukami,K.: "Identification of a PIP2-binding site in chicken skeletal muscle a-actinin" J.Biol.Chem.271. 2646-2650 (1996)
[文献書誌] Moriya,S.: "PDGF activates protein kinase Cεthrough redundant and independent signaling pathway involving phospholipase C γor phosphatidylinositol 3-kinase" proc.Natl.Acad.Sci.USA. 93. 151-155 (1996)
[文献書誌] Matushima,H.: "Changes in platelet phospholipase C protein level and activity in Alzheimer's disease" Neurobiol.of Aging. 16. 895-900 (1996)
[文献書誌] Miura,K.: "Interaction of Ash/Grb2 via its SH3 domains with neuron-specific p150 and p65" Biochem.J.316. 639-645 (1996)
[文献書誌] Matsuda,M.: "Interaction between the amino-terminal SH3 domain of Crk and its natural target proteins" J.Biol.Chem.271. 14468-14472 (1996)
[文献書誌] Miki,H.: "A novel actin-depolymerizing protein N-WASP regulates the cortical cytoskeletal rearrangement in a PIP2 dependent manner at the downstream of tyrosine Kinase" EMBO J.15. 5326-5335 (1996)
[文献書誌] Matsuzaki,H.: "Isolation of the active form of RAC-protein kinase from transfected COS-7 cells treated with heat shock stress and effects of phosphatidylinositol 3,4,5-triphosphate and phosphatidylinositol 4,5-bisphosphate on its enzyme activity" FEBC Lett.396. 305-308 (1996)
[文献書誌] Itoh,T.: "b-Tubulin binds Src homology 2 domains through a region different from the tyrosine-phosphorylated protein-recognizing site" J.Biol.Chem.271. 27931-27935 (1996)
[文献書誌] Miki,H.: "Tyrosine Kinase signalling regulates WASP function, which is essntial for megakaryocyte differentiation" Cell Grwoth Differentiation. 8. 195-202 (1997)
[文献書誌] Takenawa,T.: "Signaling through Grb2/Ash-control of the Ras Pathway and the cytoskeleton" Current Topic Microbiol.Immunol.(in press). (1997)
[文献書誌] Houssa,B.: "Cloniong of a novel human diacylglycerol kinase containing three cystein-rich domains,a proline-rich region and a pleckstrin homology domain with overlapping ras-associating domain" J.Biol.Chem.(in press). (1997)
[文献書誌] Sakisaka,T.: "Phosphatidylinositol 4,5-bisphosphate phosphatase regulates the rearrangement of actin filaments" Mol.Cell Biol.(in press). (1997)
[文献書誌] Fukuoka,M.: "Identification of N-WASP homologs in human tra brain" Gene. (in press). (1997)
[文献書誌] Kuramochi,S.: "Molecular cloning and characterization of Byp,a murine receptor-type tyrosine phosphatase similar to human DEP-1." FEBS Lett.378. 7-14 (1996)
[文献書誌] Li,B.: "The catalytic activity of mSos guanine nucleotide exchanger is activated by Fyn TPk and T-cell antigen receptor in T-Cells." Proc.Natl.Acad.Sci.USA. 93. 1001-1005 (1996)
[文献書誌] Tokai,N.: "Kid,a novel kinesin-like DNA binding protein,is colocalized with the chromosomes during mitosis." EMBO J.15. 457-467 (1996)
[文献書誌] Onda,M.: "ErbB-2 expression is correlated with poor prognosis in osteosarcomas." Cancer. 77. 71-78 (1996)
[文献書誌] Fusaki,N.: "Physical and functional interactions of protein tyrosine kinases,p59fyn and ZAP-70,in T cell signaling." J.Immunol.156. 1369-1377 (1996)
[文献書誌] Kondo,M.: "Molecular cloning of Xenopus activin type I receptor and the analysis of its expression during embryogenesis Biochem." Biophys.Res.Commun.218. 549-555 (1996)
[文献書誌] Matsuda,S.: "Tob, a novel protein that interacts with p185erbB2,is associated with anti-proliferative activity." Oncogene. 12. 705-713 (1996)
[文献書誌] Yasunaga,M.: "Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor." J.Cell Biol.132. 91-99 (1996)
[文献書誌] Tezuka,T.: "Physical and functional association of the Cbl proto-oncogene product with a Src-family protein tyrosine kinase, p53/56lyn,in the B cell antigen receptor-mediated signaling." J.Exp.Med.183. 675-680 (1996)
[文献書誌] Shiio,Y.: "Activation of the retinoblastoma gene expression by Bcl-3 : Impication for muscle cell differentiation" Oncogene. 12. 1837-1845 (1996)
[文献書誌] Fujimoto,J.: "Characterization of the transforming activity of p80,a hyperphosphorylated protein in a Ki-1 lymphoma cell line with t(2 ; 5)" Proc.Natl.Acad.Sci.USA. 93. 4181-4186 (1996)
[文献書誌] Ilic,D.: "Impairment of mobility in endodermal cells by FAK deficiency." Exp.Cell Res.222. 298-303 (1996)
[文献書誌] Kanazawa,S.: "p59 fyn-p125 FAK cooperation in development of CD4+ CD8+ thymocytes." Blood. 187. 865-870 (1996)
[文献書誌] Asaoka,Y.: "Lipid signaling for protein kinase C activation in Handbook of Lipid Research,8,Lipid Second Messengers" Bell,R.M.,Prescott,S.M.,Exton,J.H.,eds., 16 (1996)
[文献書誌] Nozawa,Y.: "Lysophospholipase-transacylase as a virulence factor in Candida albicans in Genes and Genomes in Medically Important Fungi" Tanaka,K.,Yamaguchi,H.,Magee,P.T.eds.Foundation for Advancement of International Science, 7 (1997)
[文献書誌] Nakashima,S.: "Role of signal-transducing phospholipase A_2,C and D in Platelet activation in Advances in Molecular and Cell Biology Series,Vol.17,The Platelet" Lapetina,E.G.ed.JAI Press Inc.,Greenwich, 22 (1996)
[文献書誌] Umeki,S.: "Adenylate and guanylate cyclase in Tetrahymena in Progress in Molecular and Subcellular Biology,Vol.17,Signaling Mechanisms in Protozoa and Invertebrares" Csaba,G.,Muller N.,eds.Springer-Verlag,Berlin, 21 (1996)
[文献書誌] Kitajima,Y.: "Lipids and dimorphism of Candida albicans and Sporothrix schencki,in Lipids of Pathogenic Fungi" Prasad,R.,Ghannoum m.A.eds. CRC Press Inc., 16 (1996)
[文献書誌] Higashida,H.: "Bradykinin B2 receptors and signal transduction analyzed in NG108-15 neuroblastoma x glioma hybrid cells,B2 receptor-transformed CHO cells and ras-transfomed NIH3T3 fibroblasts,in Progress in Brain Research,Vol.112" Kumazawa,T.,kruger,L.,Mizunuma,K.eds.Elsevier Science Publisher B.V., 16 (1996)
[文献書誌] Nakashima,S.: "Platelet phospholipase C,D.in Handbook of Experimental pharmacology,Vol.126,Platelets and their factors" Bruchhausan,V.,Walter,U.,eds.Springer-Verlag,Heiderberg, 16 (1996)
[文献書誌] Takenawa,T.: "Signal transductions of SH2/SH3 : Ash/Grb2 downstream signals in Intracellular Signal Transduction,Advance in Pharmacology,Vol.36" Narin,A.,Hidaka,H.eds., 15 (1996)
[文献書誌] Ohno,S.: "The distinct biological potential of PKC isotypes in Protein Kinase C" Parker,P.J.,Dekker,l.V.,eds.R.G.Lands Company,Springer, 19 (1996)
[文献書誌] Yoneda,Y.: "Molecular mechanism of nucleocytplasmic transport of proteins through the nuclear membrane in Membrane protein : Structure,Function and Expression Control" Karger Medical and Scientific Publishers (in press), (1997)
[文献書誌] Imamono,N.: "Import and export of proteins at the nucleus in protein Targeting" Phoenix,D.ed.,Portland Press,London (in press), (1997)
[文献書誌] Wakasugi,H.: "The elevated serum level of thioredoxin in patients with malignant diseases and chronic inflammatory diseases in Oxidative Stress,Cancer,AIDS,and Neurodegenrative Diseasea" Montagnier,L.,Olivier,R.,Pasquier,C.eds.,Marcel Dekker,Inc. (in press), (1997)
[文献書誌] Yamabe,H.: "Peripheral and Central Oxygen Extractiion in Chronic Heart Failure In Exercise Gas Exchange in Heart Desease" Armonk,N.Y.ed.Futura Publishing Company, 14 (1997)
[文献書誌] Kawashima,S.: "Nitric oxide and the heat ; Implication in Physiolgical and Pathological conditions In Cardiac-Vascular Remodeling and Function Interaction" Maruyama,Y.ed.Verlag, 13 (1996)
[文献書誌] Kita,T.: "Lysophosphatidylcholine induced gene expression of endothelial platelet-derived growth factor-β-chain and intercellular adhesion molecule-1." Medical Science Symposia Series (in press), (1997)
[文献書誌] Sakai,A.: "P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits prior to intimal accumulation of Macrophages and T-lymphocytes." Arteriosclerosis,Thrombosis,and Vascular Biology (in press), (1997)

1996 年度 実績報告書

細胞内情報伝達機構網の研究

研究代表者

西塚 泰美 神戸大学, 学長 (10025546)

研究成果

[文献書誌] Nakamura,S.: "Mammalian phospholipase D : Phosphatidylethanolamine as an essential component." Proc.Natl.Acad.Sci.USA. 93. 4300-4304 (1996)

[文献書誌] Shimooku,K.: "Reconstitution of GTP-γ-S-dependent phospholipase D activity with ARF,RhoA,and a soluble 36-kDa protein." FEBS Lett.387. 141-144 (1996)

[文献書誌] Nakamura,S.: "Phoshatidylcholine hydrolysis and protein kinase Cactivation for intracellular signaling network." J.Lipid Mediators Cell Signalling. 14. 197-202 (1996)

[文献書誌] 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 translocation upon fertilization." J.Biol.Chem.271. 13250-13257 (1996)

[文献書誌] Tokmakov,A.: "Phosphoregulatory tyrosine of Xenopus MAP kinase is out of the reach of the enzyme's catalytic center after autophosporylation. Biochemical evidence for conformational changes upon phosphorylation." Eur.J.Biochem.241. 322-329 (1996)

[文献書誌] Fukami,Y.: "Activation and translocation of a Src-family protein tyrosine kinase in fertilized Xenopus eggs." J.Reprod. & Develop.43 (in press). (1997)

[文献書誌] Fukasawa,M.: "SRB1,a class B scavenger receptor,recognizes both negatively charged liposomes and apoptotic cells." Exp.Cell Res.222. 246-250 (1996)

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

[文献書誌] Hara,N.: "Lysophosphatidylserine enhances exogenous type II phospholipase A2-induced activation of rat serosal mast cells." Biol.Pharm.Bull.19. 474-476 (1996)

[文献書誌] Kim,H.S.: "Age-related changes of a-tocopherol transfer protein expression in rat liver." J.Nutr.Sci.Vitaminol.42. 11-18 (1996)

[文献書誌] Emoto,K.: "Redistribution of phosphatidylethanolamine at the cleavage furrow of dividing cells during cytokinesis." Proc.Natl.Acad.Sci.USA. 93. 12867-12872 (1996)

[文献書誌] Matsuzawa,A.: "Release of secretory phospholipase A2 from rat neuronal cells and its possible function in the regulation of catecholamine secretion." Biochem.J.318. 701-709 (1996)

[文献書誌] Lan,F.: "Extended fitness of variable region primers by a novel PCR protocol." J.Immunol.Methods. 195. 27-32 (1996)

[文献書誌] Hattori,K.: "cDNA cloning and expression of intracellelar platelet-activating factor (PAF) acetylhydrolase II." J.Biol.Chem.271. 33032-33038 (1996)

[文献書誌] Hattori,M.: "PAF and PAF acetylhydrolase in the nervous system." J.Lipid Mediators Cell Signalling. 14. 99-102 (1996)

[文献書誌] Albrecht,U.: "Platelet-activating factor acetylhydrolase expression and activity suggest a link between neuroral migration and platelet-activating factor." Devel.Biol.180. 579-593 (1996)

[文献書誌] Kudo,I.: "Function of type II phospholipase A2 in dopamine secretion by rat neuronal PC12 cells." J.Lipid Mediators Cell Signalling. 14. 25-31 (1996)

[文献書誌] Ho,Y.S.: "Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer." Nature. 385. 89-93 (1996)

[文献書誌] Sato,T.: "Serine Phospholipid-specific phospholipase A that is secreted from activated platelets" J.Biol.Chem.272. 2192-2198 (1997)

[文献書誌] Ueda,N.: "Induction of cyclooxygenase-1 in a human megakaryoblastic cell line (CMK) differentiated by phorbol ester." Biochim.Biophys.Acta.1344. 103-110 (1997)

[文献書誌] Harada,Y.: "Role of prostaglandin H synthase-2 in prostaglandin E2 formation in rat carrageenininduced pleurisy." Prostaglandins. 51. 19-33 (1996)

[文献書誌] Ikawa,H.: "Arachidonate 12-lipoxygenase in porcine anterior pituitary cells : its localization and possible function in gonadotrophs." J.Endocrinol.148. 33-41 (1996)

[文献書誌] Nakamura,M.: "Subcellular localization of arachidonate 12-lipoxygenase and morphological effect of its overexpression on murine kerationcyes." Cell Tissue Res.(in press). (1997)

[文献書誌] Nishioka,N.: "Gene of rat Ca^<2+>/calmodulin-dependent protein kinase IIα isoform cloning and whole structure." FEBS LEtt.396. 333-336 (1996)

[文献書誌] Ueda,N.: "Enzymes for anandamide biosynthesis and metabolism." J.Lipid Mediators Cell Signalling. 14. 57-61 (1996)

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

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

[文献書誌] Nakashima,S.: "Molecular cloning of Δ9 fatty acid desaturase from protozoan Tetrahymena thermophila and its mRNA expression during thermal membrane adaptation." Biochem.J.317. 29-34 (1996)

[文献書誌] Liu,B.: "PLD activation in Chinese hamster ovary (CHO) cells transfected with PGF2 αreceptor cDNA." Prostaglandins. 51. 233-248 (1996)

[文献書誌] Adachi,T.: "Mitogenactivated protein kinase activation in hepatocyte growth factor-stimulated rat hepatocytes : Involvement of protein tyrosine kinase and protein kinase C." Hepatology. 23. 1244-1253 (1996)

[文献書誌] Kovacs,P.: "Phospholipase D activity in the Tetrahymena pyriformis." Biochem.Biophys.Res.Commun.222. 359-361 (1996)

[文献書誌] Banno,Y.: "Differential translocation of phospholipase C isozymes to integrin-mediated cytoskeletal complexes in thrombin^stimulated human platelets." J.Biol.Chem.271. 14989-14994 (1996)

[文献書誌] Kumada,T.: "Phenylarsine oxide (PAO)-mediated activation of phospholipase D in rat basophilic leukemia (RBL-2H3) cells : Possible involvement of calcium and protein kinase C." Immunobiology. 195. 347-359 (1996)

[文献書誌] Sakai,H.: "Suppressed expression of CD44 variant isoforms during human glioma A172 cell differentiation induced by cyclic AMP." Neurosci.Lett.210. 189-192 (1996)

[文献書誌] Nagata,K.: "Protein Kinase C isozymes in human megakaryoblastic leukemia cell line,MEG-01 : Possible involvement ot the isozymes in the differentiation process of MEG-01 cells." Br.J.Haematol.93. 762-771 (1996)

[文献書誌] Ojio,K.: "Effect of Clostridium difficile toxin B on IgE receptor-mediated signal transduction in rat basophilic leukemia cells : inhibition of phospholipase D activation." Biochem.Biophys.Res.Commun.224. 591-596 (1996)

[文献書誌] Alam,S.: "Molecular cloning a gene encoding acid α-glucosidase from Tetrahymena pyriformis." J.Eukaryot.Microbiol.43. 295-303 (1996)

[文献書誌] Nakamura,Y.: "Brefeldin A inhibits antigen-or calcium ionophore-stimulated but not PMA-induced phospholipase D activation in raty basophilic leukemia (RBL-2H3) cells." Immunobiology. 195. 231-242 (1996)

[文献書誌] Yoshimura,S.: "Differential mRNA expression of phospholipase D (PLD) isozymes during cAMP-induced differentiatiion in C6 glioma cells." Biochem.Biophys.Res.Commun.225. 494-499 (1996)

[文献書誌] Banno,Y.: "Membrane-associated phospholipase D activity in neural cell line PC12." J.Lipid Mediators Cell Signaling. 14. 237-243 (1996)

[文献書誌] Mirbod,F.: "Molecular cloning of a gene encod translation initiatiion factor (TIF) from C.albicans." J.Med.Vet.Mycol.34. 393-400 (1996)

[文献書誌] Ohguchi,K.: "Effect of Clostridium difficile Toxin A and Toxin B on Phospholipase D activation in human promyelocytic leukemic HL60 cells." Infect.Immun.64. 4433-4437 (1996)

[文献書誌] Hashii,M.: "Bradykinin-activated two signal pathways of protein tyrosine phosphorylation and formation of inositol tetrakisphosphates merge at the Ca^<2+> influx process in ras-transformed NIH3T3 fibroblast cells." Biochem.J.319. 649-656 (1996)

[文献書誌] Adachi,T.: "Phospholipase D activation in hepatocyte growth factor-stimulated rat hepatocytes ; Implication in the expressions of c-jun and c-fos." Hepatology. 24. 1274-1281 (1996)

[文献書誌] Shirato,L.: "Down regulation of protein kinase C during growth enhancement induced by interleukin-6 on a human myeloma cell line,KMS-11." Cancer Lett.107. 131-136 (1996)

[文献書誌] Zhao,Y.: "Molecular cloning of dalta 9 fatty acid desaturase and growth associated chages in its mRNA expression in Tetrahymena pyriformis" Eur.J.Protistol.32. 539-544 (1996)

[文献書誌] Ohguchi,K.: "Enhancement of phospholipase D activity during differentiation in human promyelocytic leukemic HL60 cells : involvement of RhoA translocation to membranes." J.Biol.Chem.272. 1990-1996 (1997)

[文献書誌] Ito,Y.: "Impllcation of Ca^<2+>-dependent protein tyrosinephosphorylation in carbachol-induced phospholipase D activation in rat pheochromocytoma PC12 cells." J.Neurochem.68. 419-425 (1997)

[文献書誌] Hammond,S.M.: "Characterization of two alternately spliced forms of phospholipase D1." J.Biol.Chem.(in press). (1997)

[文献書誌] Nakashima,S.: "Differential expression of protein kinase C isozymes and small GTP-binding proteins during HL-60 cells differentiation by retinoic acid and cyclic AMP : Relation with phospholipase D (PLD) activation." Immunobiology. (in press). (1997)

[文献書誌] Yoshimura,S.: "Differential expression of rho family GTP-binding proteins and protein kinase C isozymes during C6 glial cell differentiation." Mol.Brain Res.(in press). (1997)

[文献書誌] Tekemura,O.S.: "Inhibition of fMLP-stimulated tyrosine phosphorylation and PLD activation by quercetin in rabbit neutrophils." Biochem.Pharmacol.(in press). (1997)

[文献書誌] Nagata,K.: "Differential expression of low Mr GTP-binding proteins in human megakaryoblastic leukemia cells,MEG-01,and their possible involvement in the differentiatiion process." Thromb.Haemost.(in press). (1997)

[文献書誌] Banno,Y.: "Nuclear ADP-ribosylation factor (ARF)-and oleate-dependent phospholipase D in rat liver cells : Increases of ARF-dependent PLD activity in regenerating liver cells." J.Biol.Chem.(in press). (1997)

[文献書誌] Mirbod,F.: "Molecular cloning of a Rho family,CDC42α gene from Candida albicans and its mRNA expression Changes during morphogenesis." J.Med.Ved.Mycol.(in press). (1997)

[文献書誌] Shiozaki,M.: "Stereocontrolled Synthesis of All Stereoisomers of the Proposed Flavolipin" Tetrahedron Lett.37. 3875-3876 (1996)

[文献書誌] Shiozaki,M.: "Synthesis of GLA-60 Positional Isomer as an LPS-Agonist and Its Activity" Chem.Lett.735-736 (1996)

[文献書誌] Saito,K.: "Immunochemical identification of the pssA gene product as phosphatidylserine synthase I of Chinese hamster ovary cells" FEBS Lett.395. 262-266 (1996)

[文献書誌] Karasawa,K.: "Cloning,Expression and Characterization of Plasma Platelet-Activating Factor-Acetylhydrolase from Guinea Pig" J.Biochem.120. 838-844 (1996)

[文献書誌] Kuge,O.: "Post-translational processing of the phosphatidylserinedecarboxylase gene product in Chinese hamster ovary cells" Biochem.J.319. 33-38 (1996)

[文献書誌] Fukasawa,M.: "Involvement of Heparan Sulfate Proteoglycans in the Bioding step for phagocytosis of Latex Beads by Chinese Hamster Ovary Cells" Exp.Cell Res.230. 154-162 (1997)

[文献書誌] Muro,M.: "Role of CD14 Molecules in Internalization of Actinobacillus actinomycetemcomitans by Macrophages and Subsequent Induction of Apoptosis" Infect.Immun.in press. (1997)

[文献書誌] Fujimoto,K.: "Transmembrane phospholipid distribution revealed by freeze-fracture replica labeling." J.Cell Sci.109. 2453-2460

[文献書誌] Shiratsuchi,A.: "Recognition of phosphatidylserine on the surface of apoptic spermatogenic cells and subsequent phagocytosis by Sertoli cells of the rat." J.Biol.Chem.272. 2354-2358 (1997)

[文献書誌] Emoto,K.: "Exposure of Phosphatidylethanolamine on the surface of apoptotic cells." Exp.Cell Res.232. in press (1997)

[文献書誌] Hashimoto,E.: "Phosphorylated Sites of Mr 25,000 Protein,a Putative Protein Phosphatase 2A Modulator,and Phosphorylation of the Synthetic Peptide Containing These Sites by Protein Kinase C." J.Biochem.119. 626-632 (1996)

[文献書誌] Qin,S.: "Cooperation of tyrosinekinases p72 syk and p53/56 lyn regulates calcium mobilization in chicken B cell oxidant strss signaling." Eur.J.Biochem.236. 443-449 (1996)

[文献書誌] Minami,Y.: "Role of protein-tyrosine kinases in stress signaling." J.Deuterium Sci.5. 11-14 (1996)

[文献書誌] Nakamura,T.: "Sigunal transduction through mk B-cell receptors on mature B cells." Immunology. 88. 593-599 (1996)

[文献書誌] Yanagi,S.: "CD45 Nodukates phosphorylation of Both Autophosphorylation and Negative Regulatory Tyrosines of Lyn in B Cells." J.Biol.Chem.271. 30487-30492 (1996)

[文献書誌] Wang,X.: "Tyrosine Phosphrylation and Syk Activation Are Involved in Thrombin-Induced Aggregation of Epinephrine-Potentiated Platelets." J.Biochem.121. 325-330 (1997)

[文献書誌] Qin,S.: "Syk-dependent and-independent Signaling Cascades in B Cells Elicited by Osmotic and Oxidative Stress." J.Biol.Chem.(in press). (1997)

[文献書誌] Liu,N.: "A new phospholipase C d4 is induced at S-phase of cell cycle and appears in nucleus" J.Biol.Chem.271. 355-360 (1996)

[文献書誌] Fukami,K.: "Identification of a PIP2-binding site in chicken skeletal muscle a-actinin" J.Biol.Chem.271. 2646-2650 (1996)

[文献書誌] Moriya,S.: "PDGF activates protein kinase Cεthrough redundant and independent signaling pathway involving phospholipase C γor phosphatidylinositol 3-kinase" proc.Natl.Acad.Sci.USA. 93. 151-155 (1996)

1996 年度実績報告書

西塚泰美神戸大学, 学長 (10025546)