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2001 Fiscal Year Final Research Report Summary

Biological functions of a lipid mediator, sphingosine 1-phosphate

Research Project

Project/Area Number 11480174
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

IGARASHI Yasuyuki  Hokkaido Univ. Grad. School of Pham., Prof., 大学院・薬学研究科, 教授 (70091965)

Co-Investigator(Kenkyū-buntansha) MOTOHASHI Takeshi  Hokkaido Univ. Grad. School of Pham., Inst., 大学院・薬学研究科, 助手 (90301952)
WADA Atsushi  Hokkaido Univ. Grad. School of Pham., Inst., 大学院・薬学研究科, 助手 (00301953)
INOKUCHI Jin-ichi  Hokkaido Univ. Grad. School of Pham., Asso. Prof., 大学院・薬学研究科, 助教授 (70131810)
Project Period (FY) 1999 – 2000
Keywordssphingolipid / bioactive lipids / sphingosine 1-phosphate / microdomain (raft) / sphingosine kinase / GPCR / receptor / lipid signaling
Research Abstract

1) Roles of Sphingosine 1 -phosphate (Sph- 1 -P) in Platelet-related blood vessel biology.
(A) By RT-PCR analysis, we identified that Edg2, 4, 6, and 7 are expressed in human platelets. (B) We purified a novel sphingosine kinase from human platelets. (C) We found for the first time that both Sph-1-P and LPA are released from activated platelets by using new two dimensional TPC separation system. (D) We showed that Sph-1-P released from activated platelets induces in vitro angiogenesis and smooth muscle cell contraction.
2) Besides so-far known sphingosine kinases (1 and 2), we identified and cloned two novel sphingosine kinases (3 and 4).
3) Activation of Rho and FAK through Edg-5 was suggested to regulate cell motility.
4) Studies on Sph-1-P receptors.
(A) We first showed that Edg 1 and Edg 6 are N-glycosylated on Asp residue and suggested the roles of glycosylyation on the receptor dynamics toward microdomain in plasmamembrane. (B) We identified ligand- binding amino acid residues in Edg-6 from computer modeling and mutant analysis.

  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Sato K.: "Possible involvement of the cell surface receptors in sphingosine 1-phosphate-induced activation of extracellular signal-regulated kinase in C6 glioma cells"Mol. Pharmacol.. 55. 126-133 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Megidish T.: "Endogenous substrates of sphingosine-dependent kinases (SDKs) are chaperone proteins : heat shock proteins glucose-regulated proteins, protein disulfide isomerase, and calreticulin"Biochemistry. 38. 3369-3378 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sweeney E. A.: "Increase in ceramide levels in normal human mesangial cells subjected to different stresses are the result of changes in distinct enzyme activities and can influence cellular responses to other stimuli"J. Biochem.. 125. 737-745 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamura S.: "Mechanism for inhibition of haptotactic motility by sphingosine 1-phosphate"Proc. JCBL. 41. 99-102 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yang L.: "Sphingosine 1-phosphate formation and intracellular Ca2+ mobilization in human platelets : Evaluation with sphingosine kinase inhibitors"J. Biochem.. 126. 84-89 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamura S.: "Sphingosine1-phosphate inhibits haptotactic motility by overproduction of focal adhesion site in B16 melanoma cells through Edg-induced activation of Rho"Ann. N. Y. Acad Sci. 905. 301-307 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Motohashi K.: "Identification of lysophospholipid receptors in human platelets: the relation of two agonists, lyso-phosphatidic acid and sphingosine 1-phosphate"FEBS Lett.. 468. 189-193 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jimbo M.: "Development of a new inhibitor of glucosylceramide synthase"J. Biochem.. 127. 485-491 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kohno T.: "Aspargine-linked glycosylation of Edg1, a receptor for sphingosine 1-phosphate : Significance in receptor internalization and receptor-coupled signaling"Chem. Phys. Lipid. 107. 39 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yatomi Y.: "Sphingosine 1-phosphate as a major bioactive lysophospholipid released from platelets and interacting with endothelial cells"Blood. 96. 3431-3438 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inokuchi J.: "Glycosphingolipid deficiency affects functional microdomain formation in Lewis lung carcinoma cells"Glycoconjugate J.. 17. 239-245 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yatomi Y.: "Sphingosine 1-phosphate : synthesis and release"Plastaglandins & other lipid mediators. 64. 107-122 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murate T.: "Cell type-specific localization of sphingosine kinase 1a in human tissues"J. Histochem. Cytochem.. 49. 845-855 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Igarashi Y.: "Production and function of a lipid mediator, sphingosine 1 -phosphate in blood, a comparison with lysophosphatidic acid"Chem. Phys. Lipid. 108. 20 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kabayama K.: "Suppression of integrin expression and tumorigenicity by sulfation of lactosylceramide in 3LL lewis lung carcinoma cells"J. Biol. Chem.. 276. 26777-26783 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 五十嵐靖之: "セカンドメッセンジャーあるいはセカンドアゴニストとしてのスフインゴシン1-リン酸研究の新しい展開"蛋白質核酸酵素. 44(7). 112-119 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 五十嵐靖之: "新しい脂質メディエーターとしてのスフインゴ脂質の役割-スフィンゴ生理学とスフィンゴ栄養学の構築をめざして-"道薬誌. 16(5). 4-11 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 和田淳: "スフィンゴシン1-リン酸の受容体"実験医学別冊号、脂質メディエーター研究の最前線. 18. 179-183 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岡崎俊朗: "スフィンゴ脂質とアポトーシス"生化学新実験講座(東京化学同人). 274-281 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato K., Tomura H., Igarashi Y., Ui, M., Okajima F.: "Possible involvement of the cell surface receptors in spningosine 1-phosphate-induced activation of extracellular signal-regulated kinase in C6 glioma cells"Mol. Pharmacol.. 55. 126-133 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Megidish T, Takio K., Titani K., Iwabuchi K., Hamaguchi A., Igarashi Y., Hakomori Si.: "Endogenous substrates of sphingosine-dependent kinases (SDKs) are chaperone proteins: heat shock proteins, glucose-regulated proteins, protein disulfide isomerase, and calreticulin"Biochemistry. 38. 3369-3378 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sweeney E. A., Igarashi Y.: "Increase in ceramide levels in normal human mesangial cells subjected to different stresses are the result of changes in distinct enzyme activities and can influence cellular responses to other stimuli"J. Biochem.. 125. 737-745 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamura S., Hakomori S., Wada A., Igarashi Y.: "Mechanism for inhibition of haptotactic motility by sphingosine 1-phosphate"Proc. JCBL. 41. 99-102 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yang L., Yatomi Y., Hisano N., Sato K., Igarashi Y., Ozaki Y.: "Sphingosine 1- phosphate formation and intracellular Ca^<2+> mobilization in human platelets: Evaluation with sphingosine kinase inhibitors"J. Biochem.. 126. 84-89 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamura S., Hakomori S., Wada A., Igarashi Y.: "Sphingosine 1-phosphate inhibits haptotactic motility by overproduction of focal adhesion site in B16 melanoma cells through Edg-induced activation of Rho"Ann. N. Y. Acad. Sci.. 905. 301-307 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motohashi K., Shibata S., Ozaki Y., Yatomi Y., Igarashi Y.: "Identification of lysophospholipid receptors in human platelets: the relation of two agonists, lyso-phosphatidic acid and sphingosine 1-phosphate"FEBS Lett.. 468. 189-193 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jimbo M., Yamaguchi K., Yamaki N., Nunomura K., Kabayama K., Igarashi Y., Inokuchi J.: "Development of a new inhibitor of glucosylceramide synthase"J. Biochem.. 127. 485-491 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kohno T., Wada A., Igarashi Y.: "Aspargine-linked glycosylation of Edg1, a receptor for sphingosine 1-phosphate : Significance in receptor internalization and receptor-coupled signaling"Chem. Phys. Lipid. 107. 39-39 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yatomi Y., Hisano N., Ge R., Kazama F., Satoh S., Igarashi Y., Kume S., Ozaki Y.: "Sphingosine 1-phosphate as a major bioactive lysophospholipid released from platelets and interacting with endothelial cells"Blood. 96. 3431-3438 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inokuchi J., Uemura S., Kabayama K., Igarashi Y.: "Glycosphingolipid deficiency affects functional microdomain formation in Lewis lung carcinoma cells"Glycoconjugate J.. 17. 239-245 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yatomi Y., Ozaki Y., Ohmori T., Igarashi Y.: "Sphingosine 1-phosphate: synthesis and release"Plastaglandins & other lipid mediators. 64. 107-122 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murate T., Banno Y., T-Koizumi K., Watanabe K., Mori N., Wada A., Igarashi Y., Takagi A., Kojima T., Asano H., Akao Y., Yoshida S., Saito H., Nozawa Y.: "Cell type-specific localization of sphingosine kinase 1a in human tissues"J. Histochem. Cytochem.. 49. 845-855 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Igarashi Y., Yatomi Y., Tigyi G.: "Production and function of a lipid mediator, sphingosine 1-phosphate in blood, a comparison with lysophosphatidic acid"Chem. Phys. Lipid. 108. 20-20 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kabayama K., Ito N., m. Honke K., Igarashi Y., Inokuchi J.: "Suppression of integrin expression and tumorigenicity by sulfation of lactosylceramide in 3LL lewis lung carcinoma cells"J. Biol. Chem.. 276. 26777-26783 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Igarashi Y.: "Recent development of sphingosine 1-phosphate studies as a second messenger or a second agonist in cell signaling"Tanpakushistu Kakusan, Koso (review in Japanese). 44 (7). 1059-1066 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Igarashi Y.: "Biological functions of sphingolipids as novel lipid mediators; towards the establishment of sphingophysiology and sphingo-nutrition"Doyakushi (review in Japanese). 16 (5). 4-11 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada A., Igarashi Y.: "Sphingosine 1-phosphate receptors"Experimental Medicine (review in Japanese). 18. 179-183 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okazaki T., Kitano T., Kondo T., Igarashi Y.: "Apoptosis by sphimgolipids"Basic Methodology in Biochemistry (Tokyo Kagaku Dozin). 274-281 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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