Physiological roles of phosphatidylinositol bisphosphates

• Project/Area Number: 18689003
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Akita University
• Principal Investigator: SASAKI Takehiko Akita University, 医学部, 教授 (50333365)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000); Fiscal Year 2008: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2006: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
• Keywords: 細胞生物学 / 脂質 / 胚発生 / 免疫 / 神経 / 貪食 / ホスファターゼ / イノシトールリン脂質 / 遺伝子改変マウス / 好中球 / 炎症

Research Abstract

イノシトールリン脂質の中でも特に、イノシトール環水酸基に二ヶ所のリン酸化を受けたホスファチジルイノシトール二リン酸に着目した解析を行った。PI(3,4)P2 とPI(3,5)P2 の代謝を司る酵素のいくつかは、胚発生に必須であることを見出した。また、臓器、組織特異的に酵素を欠損する遺伝子改変マウスを用いた表現型解析によって、PI(3,4)P2 が、神経系、免疫系、また発癌に関わること、さらに、PI(3,5)P2 の生成、分解を触媒する酵素が、上皮細胞、神経細胞において果たす役割を新たに見出した。

Research Products

• [Journal Article] Sequential Regulation of DOCK2 Dynamics by Two Phospholipids during Neutrophil Chemotaxis. (2009)
  • Author(s): Nishikimi, A., Fukuhara, H., Su, W., Hongu, T., Takasuga, S., Mihara, H., Cao, Q., Sanematsu, F., Kanai, M., Hasegawa, H., Tanaka, Y., Shibasaki, M., Kanaho, Y., Sasaki, T., Frohman, M.A., Fukui Y.
  • Journal Title: Science 324 Pages: 384-387
  • Peer Reviewed
• [Journal Article] Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages. (2009)
  • Author(s): Mogi C, Tobo M, Tomura H, Murata N, He XD, Sato K, Kimura T, Ishizuka T, Sasaki T., Sato T, Kihara Y, Ishii S, Harada A, & Okajima F.
  • Journal Title: J. Immunol 182 Pages: 3243-3251
  • Peer Reviewed
• [Journal Article] Allergic airway hyperresponsiveness,inflammation, and remodeling do not develop in phosphoinositide 3-kinase γ -deficient mice. (2009)
  • Author(s): Takeda, M., Ito, W., Tanabe, M., Ueki, S., Kato, H., Kihara, J., Tanigai, T., Chiba, T., Yamaguchi, K., Kayaba, H., Imai, Y., Okuyama, K., Ohno, I., Sasaki, T. & Chihara, J.
  • Journal Title: 123 Pages: 805-812
  • Peer Reviewed
• [Journal Article] Sequential Regulation of DOCK2 Dynamics by Two Phospholipids during Neutrophil Chemotaxis (2009)
  • Author(s): Nishikimi, A. et.al.
  • Journal Title: Science 324 Pages: 384-387
  • Peer Reviewed
• [Journal Article] Loss of PIP5KI ・ demonstrates that PIP5KI isoform-specific PIP2 synthesis is required for IP3 formation. (2008)
  • Author(s): Wang, Y., Chen, X., Lian, L., Tang, T., Stalker, T., Sasaki, T., Brass, L., Choi, J., Hartwig, J. & Abrams, C.
  • Journal Title: Proc. Natl. Acad. Sci 105 Pages: 14064-14069
  • Peer Reviewed
• [Journal Article] A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN dephosphorylates phosphatidylinositol 4,5-bisphosphate. (2008)
  • Author(s): Iwasaki, H., Murata, Y., Kim, Y., Hossain, M., Worby, C., Dixon, J., McCormack, T., Sasaki, T. & Okamura, Y.
  • Journal Title: Proc. Natl. Acad.Sci 105 Pages: 7970-7975
  • Peer Reviewed
• [Journal Article] IGF-I secreted by osteoblasts acts as a poteint chemotactic factor for osteoblast. (2008)
  • Author(s): Nakasaki, M, Yoshioka, K, Miyamoto, Y, Sasaki, T., Yoshikawa, H. & Itoh, K.
  • Journal Title: Bone 43 Pages: 869-879
  • Peer Reviewed
• [Journal Article] Pten deficiency in melanocytes results in resistance to hair graying and susceptibility to carcinogen-induced melanomagenesis. (2008)
  • Author(s): noue-Narita, T., Hamada, K., Sasaki, T., Hatakeyama, S., Fujita, S., Kawahara, K., Sasaki, M., Kishimoto, H., Eguchi, S., Kojima, I., Beermann, F., Kimura, T., Osawa, M., Itami, S., Mak, T., Nakano, T., Manabe, M. & Suzuki, A.
  • Journal Title: Cancer Res 68 Pages: 5760-5768
  • Peer Reviewed
• [Journal Article] Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages. (2008)
  • Author(s): Kuroda, S., Nishio, M., Sasaki, T., Horie, Y., Kawahara, K., Sasaki, M., Natsui, M., Matozaki, T., Tezuka, H., Ohteki, T., Forster, I., Mak, T., Nakano, T.& Suzuki, A.
  • Journal Title: Eur J. Immunol 38 Pages: 1131-1140
  • Peer Reviewed
• [Journal Article] CD28 provides T cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer. (2008)
  • Author(s): Garcon, F., Patton, D., Emery, J., Hirsch, E., Rottapel, R., Sasaki, T. & Okkenhaug, K.
  • Journal Title: Blood 111 Pages: 1464-1471
  • Peer Reviewed
• [Journal Article] Loss of PIP5KIγ, unlike other PIP5KI isoforms, impairs the integrity of the membrane cytoskeleton in murine megakaryocytes. (2008)
  • Author(s): Wang, Y., Litvinov, R., Xinsheng, D., Bach, T., Lian, L., Petrich, B., Monkley, S., Critcheley, D., Sasaki, T., Birnbaum, M., Weisel, J., Hartwig, J.& Abrams, C.
  • Journal Title: J. Clin. Invest 118 Pages: 812-819
  • Peer Reviewed
• [Journal Article] Critical roles of the p110β subtype of phosphoinositide 3-kinase in lipopolysaccharide-induced Akt activation and negative regulation of nitrite production in RAW 264.7 cells. (2008)
  • Author(s): Tsukamoto, K., Hazeki, K., Hoshi, M., Nigorikawa, K., Inoue. N., Sasaki, T. & Hazeki, O.
  • Journal Title: J. Immunol 180 Pages: 2054-2061
  • Peer Reviewed
• [Journal Article] The phosphoinositide-3 kinase-γ - Akt pathway mediates renal tubular injury in cisplatin nephrotoxicity. (2008)
  • Author(s): Kuwana, H., Terada, Y., Kobayashi, T., Okado, T., Penninger, J., Sasaki, J., Sasaki, T. & Sasaki, S.
  • Journal Title: Kidney Int 73 Pages: 430-445
  • Peer Reviewed
• [Journal Article] A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN dephosphorylates phosphatidylinositol4, 5-bisphosphate (2008)
  • Author(s): Iwasaki, H. et.al.
  • Journal Title: Proc. Natl. Acad. Sci. 105 Pages: 7970-7975
  • Peer Reviewed
• [Journal Article] CD28 provides T cell costimulation and enhances PI3K activity at the immune synanse independently of its canacity to interact with the p85/p110 heterodimer (2008)
  • Author(s): Garcon, F. et.al.
  • Journal Title: Blood 111 Pages: 1464-1471
  • Peer Reviewed
• [Journal Article] Regulation of FcγR-stimulated phagocytosis by the 72 kDa inositol polyphosphate 5-phosphatase. (2007)
  • Author(s): Horan K., Watanabe K., Kong A., Bailey C., Rasko J., Sasaki T. & Mitchell C.
  • Journal Title: Blood 110 Pages: 4480-4491
  • Peer Reviewed
• [Journal Article] Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas. (2007)
  • Author(s): Yanagi, S., Kishimoto, H., Kawahara, K., Sasaki, T., Sasaki, M., Nishio, M., Yajima, N., Hamada, K., Horie, Y., Kubo, H., Mak, T., Nakano, T., Nakazato, M. & Suzuki, A.
  • Journal Title: J. Clin. Invest 117 Pages: 2929-2940
  • Peer Reviewed
• [Journal Article] Interaction between telencepalin and ERM family proteins mediates dendritic filopodia formation. (2007)
  • Author(s): Furutani Y., Matsuno H., Kawasaki M., Sasaki T., Mori K., Yoshihara Y.
  • Journal Title: J. Neurosci 27 Pages: 8866-8876
  • Peer Reviewed
• [Journal Article] The Pten/PI3K pathway governs the homeostasis of V ・14 iNKT cells. (2007)
  • Author(s): Kishimoto H., Ohteki T., Yajima N., Kawahara K., Natsui M., Kawarasaki S., Hamada K., Horie Y., Kubo Y., Arase S., Taniguchi M., Vanhaesebroeck B., Mak T., Nakano T., Koyasu S., Sasaki T. & Suzuki A.
  • Journal Title: Blood 109 Pages: 3316-3324
  • Peer Reviewed
• [Journal Article] PI(3)Kγ has an important context-dependent role in chemokinesis. (2007)
  • Author(s): Ferguson J., Milne L., S. Kulkarni, Sasaki T., Walker S., Andrews S., Crabbe T., Finan P., Jones G., Jackson S., Camps M., Rommel C., Wymann M., Hirsch E., Hawkins P. & Stephens L.
  • Journal Title: Nature Cell Biol 9 Pages: 86-91
  • Peer Reviewed
• [Journal Article] Control of cell polarity and motility by the PI(3,4,5)P3 phosphatase SHIP1. (2007)
  • Author(s): Nishio, M., Watanabe, K., Sasaki, J., Taya, C., Takasuga, S., Iizuka, R., Balla T., Yamazaki M., Watanabe H., Itoh R., Kuroda S., Horie Y., Forster I., Mak T., Yonekawa H., Penninger J., Kanaho Y., Suzuki A. & Sasaki T.
  • Journal Title: Nature Cell Biol 9 Pages: 36-44
  • Peer Reviewed
• [Journal Article] Non-invasive visualization of the lipid product of class I PI3K in transgenic mouse models. (2007)
  • Author(s): Sasaki, T., et. al.
  • Journal Title: Biochem. Soc.Trans. 35 Pages: 245-248
  • Peer Reviewed
• [Journal Article] The physiology of phosphoinositides. (2007)
  • Author(s): Sasaki, T., et. al.
  • Journal Title: Biol. Pharm. Bull. 9 Pages: 1599-1604
  • NAID: 110006380235
  • Peer Reviewed
• [Journal Article] Regulation of FcγR-stimulated phagocytosis by the 72 kDa inositol polyphosphate 5-phosphatase (2007)
  • Author(s): Horan, K., et. al.
  • Journal Title: Blood 110 Pages: 4480-4491
  • Peer Reviewed
• [Journal Article] Control of cell polarity and motility by the PI(3,4,5)P_3 phosphatase SHIP1. (2007)
  • Author(s): Nishio, M.
  • Journal Title: Nature Cell Biol. 9 Pages: 36-44
• [Journal Article] PI(3)Kγ has an important context-dependent role in chemokinesis. (2007)
  • Author(s): Ferguson J.
  • Journal Title: Nature Cell Biol. 9 Pages: 86-91
• [Journal Article] DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. (2006)
  • Author(s): Kunisaki, Y., Nishikimi, A., Tanaka, Y., Takii, R., Noda, M., Inayoshi, A., Watanabe, K., Sasazuki, T., Sasaki, T. & Fukui, Y.
  • Journal Title: J. Cell Biol 174 Pages: 647-652
  • Peer Reviewed
• [Journal Article] Hyperplasia and carcinomas in Pten-deficient mice and reduced PTEN protein in human bladder cancer patients. (2006)
  • Author(s): Tsuruta, H., Kishimoto, H., Sasaki, T., Natsui, M., Shibata, Y., Tsuchiya, N., Horie, Y., Hamada, K., Yajima, N., Enomoto, K., Gordon, J., Mak, T., Nakano, T., Habuchi, T. & Suzuki, A.
  • Journal Title: Cancer Res 66 Pages: 8389-8396
  • Peer Reviewed
• [Journal Article] Crucial role of the small GTPase ARF6 in hepatic cord formation during liver development. (2006)
  • Author(s): Suzuki, T, Kanai, Y., Hara, T., Sasaki, J., Sasaki, T., Kohara, M., Maehama, T., Taya, C., Shitara, H., Yonekawa, H., Frohman, M., Yokozeki, T. & Kanaho, Y.
  • Journal Title: Mol. Cell. Biol 26 Pages: 6149-6156
  • Peer Reviewed
• [Journal Article] Src homology 2 (SH2)-containing 5'-inositol phosphatase localizes to podosomes, and the SH2 domain is implicated in the attenuation of bone resorption in osteoclasts. (2006)
  • Author(s): Yogo, K., Mizutamari, M., Mishima, K., Takenouchi, H., Ishida-Kitagawa, N., Sasaki, T. & Takeya, T.
  • Journal Title: Endocrinology 147 Pages: 3307-3317
  • Peer Reviewed
• [Journal Article] Hepatic gene expression in hepatocyte-specific Pten deficient mice showing steatohepatitis without ethanol challenge. (2006)
  • Author(s): Sato W, Horie Y, Kataoka E, Ohshima S, Dohmen T, Iizuka M, Sasaki J, Sasaki T, Hamada K, Kishimoto H, Suzuki A, Watanabe S.
  • Journal Title: Hepatol. Res 34 Pages: 256-265
  • NAID: 10020405034
  • Peer Reviewed
• [Journal Article] Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-・ and PTEN. (2006)
  • Author(s): Zhao, M., Song, B., Pu, J., Wada, T., Reid, B., Tai, G., Wang, F., Guo, A., Walczysko, P., Gu, Y., Sasaki, T., Suzuki, A., Forrester, J., Bourne, H., Devreotes, P., McCaig, C. & Penninger, J.
  • Journal Title: Nature 442 Pages: 457-460
  • Peer Reviewed
• [Journal Article] Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTEN (2006)
  • Author(s): Zhao, M.
  • Journal Title: Nature 442 Pages: 457-460
• [Journal Article] Crucial role of the small GTPase ARF6 in hepatic cord formation during liver development. (2006)
  • Author(s): Suzuki, T
  • Journal Title: Mol.Cell.Biol. 26 Pages: 6149-6156
• [Journal Article] Hyperplasia and carcinomas in Pten-deficient mice and reduced PTEN protein in human bladder cancer patients. (2006)
  • Author(s): Tsuruta, H.
  • Journal Title: Cancer Res. 66 Pages: 8389-8396
• [Journal Article] DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. (2006)
  • Author(s): Kunisaki, Y.
  • Journal Title: J.Cell Biol. 174 Pages: 647-652
• [Presentation] In vivo Role of Inositol Polyphosphate Phosphatase 4A Keystone (2009)
  • Author(s): 佐々木雄彦
  • Organizer: Symposium "PI3-Kinase Signaling in Disease"
  • Place of Presentation: Olympic Valley, CA, USA
  • Year and Date: 2009-04-25
• [Presentation] 神経細胞におけるL-PIPase の機能 (2008)
  • Author(s): 佐々木雄彦
  • Organizer: 第31 回日本分子生物学会大会 第 81 回日本生化学会大会合同大会 BMB2008 シンポジウム「リン脂質シグナリングと生体膜のダイナミクス」
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 神経細胞におけるL-PIPaseの機能 (2008)
  • Author(s): 佐々木雄彦
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Regulation of neutrophil chemotaxis by cellular lipids (2008)
  • Author(s): 佐々木雄彦
  • Organizer: 42nd Annual Scientific Meeting of the European Society for Clinical Investigation"Phagocyte biology:Molecular basis of innate immunity and chronic inflammation"
  • Place of Presentation: Geneva、 Switzerland
  • Year and Date: 2008-03-26
• [Presentation] Control of chemotaxis by cellular lipids (2008)
  • Author(s): Sasaki, T.
  • Organizer: 42nd meeting of the European Society for Clinical Investigation
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 2008-03-26
• [Presentation] 神経細胞におけるL-PIPaseの機能 (2007)
  • Author(s): 佐々木雄彦
  • Organizer: 第30 回日本分子生物学会大会 第80 回日本生化学会大会合同大会「細胞制御のオーガナイザーとしてのホスファターゼスーパーファミリー」ワークショップ
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Roles of 3-phosphorylated phosphoinositides (2007)
  • Author(s): 佐々木雄彦
  • Organizer: 第40回 日本発生生物学会 ・ 第59回 日本細胞生物学会 合同大会、ミニシンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2007-05-30
• [Presentation] イノシトールリン脂質代謝異常による細胞空胞化 (2006)
  • Author(s): 佐々木雄彦
  • Organizer: 日本分子生物学会2006フォーラム、メンブレントラフィックの奔流-分子から機能へ-、シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2006-12-06
• [Presentation] Role of Phosphoinositide Phosphatase in Neutrophil Migration (2006)
  • Author(s): 佐々木雄彦
  • Organizer: Biochemical Society Focused Meeting、"3rd Focused Meeting on PI3K signalling and disease"、シンポジウム
  • Place of Presentation: Bath, UK
  • Year and Date: 2006-11-07
• [Presentation] Role of Phosphoinositide Phosphatase in Neutrophil Chemotaxis (2006)
  • Author(s): 佐々木雄彦
  • Organizer: The 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress "New aspects of phosphoinositide signaling"、シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2006-06-21
• [Presentation] ホスホイノシタイドキナーゼ/ホスファターゼのマウス個体における機能 (2006)
  • Author(s): 佐々木雄彦
  • Organizer: 第48回日本脂質生化学会総会、シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2006-06-08
• [Book] PtdIns(3, 4, 5)P3代謝酵素による好中球遊走の制御経路の役割 (2007)
  • Author(s): 西尾美希・鈴木聡・佐々木雄彦
  • Total Pages: 2
  • Publisher: 秀潤社
• [Book] 形と運動を司る細胞のダイナミクス 脂質結合モジュールによるイノシトールリン脂質動態解析 (2006)
  • Author(s): 佐々木雄彦
  • Total Pages: 6
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~bisei/index.html
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~bisei/index.html