Molecular mechanism of inhibition of cell motility

• Project/Area Number: 16590163
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: Kanazawa University Graduate School of Medicine
• Principal Investigator: SUGIMOTO Naotoshi Kanazawa University Graduate School of Medicine, Department of Vascular Molecular Physiology, Assistant Professor, 医学系研究科, 講師 (80272954)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: sphingosine-1-phosphate / cell migration / signal transduction / small G protein

Research Abstract

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces a variety of biological responses in diverse cell types. Many of these responses are mediated by S1P receptors, S1P_1/EDG1, S1P_3/EDG3, and S1P_2/EDG5. We previously showed that S1P_2/EDG5, via G_<12> and G_<13> proteins, mediated inhibiton of insulin-like growth factor-I (IGF-I)-induced Rac activation and cell migration, whereas S1P_1/EDG1 and S1P_3/EDG3 each alone, via G_1 protein, mediated Rac activation and stimulation of cell migration. However, it is not known how G_<12> and G_<13> proteins mediate inhibition of Rac and cell migration in S1P_2/EDG5 signaling. We found that the pretreatment with C3 toxin, which inactivates Rho, and the expresson of dominat negative Rho A prevented S1P_2/EDG5-mediated inhibition of Rac and cell migration. On other hand, the expression of constitutively active Rho inhibited IGF-I induced Rac activation and cell migration. However, Rho kinase inhibitors did not affect S1P_2/EDG5-mediated inhibition of Rac or cell migration. These results indicate that Rho, but not Rho kinase, mediates inhibition of Rac activity and cell mobility on stimulation of S1P_2/EDG5.

Research Products

• [Journal Article] Rho-dependent, Rho kinase-independent inhibitory regulation of Rac and cell migration by LPA1 receptor in Gi-inactivated CHO cells. (2006)
  • Author(s): Sugimoto N, Takuwa N, Yoshioka K, Takuwa Y.
  • Journal Title: Exp Cell Res. (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Class II phosphoinositide 3-kinase alpha-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle. (2006)
  • Author(s): Wang Y, Yoshioka K, Azam MA, Kimura T, Kuwaki T, Takuwa Y.
  • Journal Title: Biochem J. 394(Pt 3) Pages: 581-592
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Rho-dependent, Rho kinase-independent inhibitory regulation of Rac and cell migration by LPA(1) receptor in G(i)-inactivated CHO cells. (2006)
  • Author(s): Sugimoto N, Takuwa N, Yoshioka K, Takuwa Y.
  • Journal Title: Exp Cell Res. (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Class II phosphoinositide 3-kinase alpha-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle. (2006)
  • Author(s): Wang Y, Yoshioka K, Azam MA, Kimura T, Sugimoto N, Kuwaki T. Takuwa Y.
  • Journal Title: Biochem J. 394(Pr 3) Pages: 581-592
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Calcium-dependent regulation of Rho and myosin phosphatase in vascular smooth muscle. (2006)
  • Author(s): Takuwa Y., Yoshioka K., Takuwa N., Azam M.A., Sugimoto N.
  • Journal Title: Biomed Rev, (In press)
• [Journal Article] Rho-dependent, Rho kinase-independent inhibitory regulation of Rac and cell migration by LPA1 receptor in Gi-inactivated CHO cells. (2006)
  • Author(s): Sugimoto N., Takuwa N., Yoshioka K.Takuwa Y.
  • Journal Title: Exp.Cell Res. (In press)
• [Journal Article] Inhibition of Rac activation as a mechanism for negative regulation of actin cytoskeletal reorganization and cell motility by cAMP. (2005)
  • Author(s): Nagasawa SY, Takuwa N, Sugimoto N, Mabuchi H, Takuwa Y.
  • Journal Title: Biochem J 385(Pt 3) Pages: 737-744
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Endogenous NO blockade enhances tissue factor expression via increased Ca2+ influx through MCP-1 in endothelial cells by monocyte adhesion. (2005)
  • Author(s): Sakamoto T., Ishibashi T., Sakamoto N., Sugimoto K., Egashira K., Ohkawara H., Nagata K., Yokoyama K., Kamioka M., Ichiki T., Sugimoto N., Kurabayashi M., Suzuki K., Takuwa Y., Maruyama Y.
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. 25(9) Pages: 2005-2011
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of the betagamma subunits of G proteins in the cAMP response induced by stimulation of the histamine H(1) receptor. (2005)
  • Author(s): Maruko T., Nakahara T., Sakamoto K., Saito M., Sugimoto N., Takuwa Y., Ishii K.
  • Journal Title: Naunyn.Schmiedebergs.Arch.Pharmacol. 372 Pages: 153-159
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Calcium-dependent regulation of Rho and myosin phosphatase in vascular smooth muscle. (2005)
  • Author(s): Takuwa Y., Yoshioka K., Takuwa N., Azam M.A., Sugimoto N.
  • Journal Title: Biomed Rev. 16 Pages: 13-21
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Thrombin-induced rapid geranylgeranylation of RhoA as an essential process for RhoA activation in endothelial cells. (2005)
  • Author(s): Ohkawara H, Ishibashi T, Sakamoto T, Sugimoto K, Nagata K, Yokoyama K, Sakamoto N, Kamioka M, Matsuoka I, Fukuhara S, Sugimoto N, Takuwa Y, Maruyama Y.
  • Journal Title: J Biol Chem. 280(11) Pages: 10182-10188
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] スフィンゴシン1リン酸受容体による癌浸潤・転移の制御とその分子機構 (2005)
  • Author(s): 多久和典子, 杉本直俊, 多久和陽
  • Journal Title: 実験医学(増刊号) 23巻6号 Pages: 218-223
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inhibition of Rac activation as a mechanism for negative regulation of actin cytoskeletal reorganization and cell motility by cAMP. (2005)
  • Author(s): Nagasawa SY, Takuwa N, Sugimoto N, Mabuchi H, Takuwa Y.
  • Journal Title: Biochem J. 385(Pr 3) Pages: 737-744
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Thrombin-induced rapid geranylgeranylation of RhoA as an essential process for RhoA activation in endothelial cells. (2005)
  • Author(s): Ohkawara H., Ishibashi T., Sakamoto T., Sugimoto K., Nagata K., Yokoyama K., Sakamoto N., Kamioka M., Matsuoka I., Fukuhar S., Sugimoto N., Takuwa Y., Maruyama Y.
  • Journal Title: J.Biol.Chem. 280(11) Pages: 10182-10188
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Endogenous NO blockade enhances tissue facto expression via increased Ca2+ influx through MCP-1 in endothelial cells by monocyte adhesion. (2005)
  • Author(s): Sakamoto T., Ishibashi T., Sakamoto N., Sugimoto K., Egashira K., Ohkawara H., Nagata K., Yokoyama K., Kamioka M., Ichiki T., Sugimoto N., Kurabayashi M., Suzuki K., Takuwa Y., Maruyama Y.
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. 25(9) Pages: 2005-2011
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Endogenous NO blockade enhances tissue factor expression via increased Ca2+ influx through MCP-1 in endothelial cells by monocyte adhesion. (2005)
  • Author(s): Sakamoto T., Ishibashi T., Sakamoto N., Sugimoto K., Egashira K., Ohkawara H., Nagata K., Yokoyama K., Kamioka M., Ichiki T., Sugimoto_N., Kurabayashi M., Suzuki K., Takuwa Y., Maruyama Y.
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. 25(9) Pages: 2005-2011
• [Journal Article] スフィンゴシン1リン酸受容体による癌浸潤・転移の制御とその分子機構 (2005)
  • Author(s): 多久和典子, 杉本直俊, 多久和陽.
  • Journal Title: 実験医学 23(6) Pages: 1014-1019
• [Journal Article] Class II phosphoinositide 3-kinase alfa-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle. (2005)
  • Author(s): Wang Y., Yoshioka K., Azam M.A., Takuwa N., Sakurada S., Kayaba Y., Sugimoto N., Inoki I., Kimura T., Kuwaki T., Takuwa Y.
  • Journal Title: Biochemical J. 394(Pt3) Pages: 581-592
• [Journal Article] Thrombin-induced rapid geranylgeranylation of RhoA as an essential process for RhoA activation in endothelial cells. (2005)
  • Author(s): H.Ohkawara et al.
  • Journal Title: J Biol Chem. (In press)
• [Journal Article] Inhibition of Rac activation as a mechanism for negative regulation of actin cytoskeletal reorganization and cell motility by cAMP (2005)
  • Author(s): SY.Nagasawa et al.
  • Journal Title: Biochem J. 385(Pt 3) Pages: 737-744
• [Journal Article] Blood lipid mediator sphingosine 1-phosphate potently stimulates platelet-derived growth factor-A and -B chain expression through S1P1-Gi-Ras-MAPK-dependent induction of Kruppel-like factor (2004)
  • Author(s): Usui S, Sugimoto N, Takuwa N, Sakagami S, Takata S, Kaneko S, Takuwa Y.
  • Journal Title: J Biol Chem. 279(13) Pages: 12300-12311
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Endogenous cryogens existing in the blood of a hypothermic patient. (2004)
  • Author(s): Shido O., Sugimoto N., Imoto T., Asai A., Maruyama M., Hara T., Watanabe T., Koizumi S.
  • Journal Title: Jpn.J.Physiol. 54(5) Pages: 449-456
  • NAID: 10014283043
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Endogenous cryogens existing in the blood of a hypothermic patient. (2004)
  • Author(s): O.Shido et al.
  • Journal Title: Jpn J Physiol. 54(5) Pages: 449-456