The integrative research for regulation by protein tyrosine phosphatases of biological functions and its molecular mechanism

2013 Fiscal Year Final Research Report

• Project/Area Number: 23370061
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kobe University
• Principal Investigator: MATOZAKI Takashi 神戸大学, 医学(系)研究科(研究院), 教授 (80252782)
• Co-Investigator(Kenkyū-buntansha): OHNISHI Hiroshi 群馬大学, 保健学研究科, 教授 (70334125)
• Co-Investigator(Renkei-kenkyūsha): MURATA Yoji 神戸大学, 医学研究科, 准教授 (60400735)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: シグナル伝達 / 生体分子 / 蛋白質 / 脳・神経 / 免疫学

Research Abstract

We have here performed the integrative research for the biological functions and molecular mechanisms for the protein tyrosine phosphatases SHP-2 as well as the related signaling pathway CD47-SIRPalpha, and R3-receptor type PTPs. We have shown that SHP-2 in the post-mitotic neurons is important for regulation of the neuronal activity. The CD47-SIRPalpha is important for regulation of dendritic cells as well as organization of lymphoid tissues. In addition, VE-PTP is implicated in regulation of endothelial cell functions by shear stress.

Research Products

• [Journal Article] Role of the protein tyrosine phosphatase Shp2 in homeostasis of the intestinal epithelium (2014)
  • Author(s): Yamashita H, Kotani T, Park JH, Murata Y, Okazawa H, Ohnishi H, Ku Y, Matozaki T
  • Journal Title: PLoSOne Volume: 9 Pages: e92904
  • DOI: 10.1371/journal.pone.0092904
  • Peer Reviewed
• [Journal Article] The CD47-SIRPα signalling system : its physiological roles and therapeutic application (2014)
  • Author(s): Murata Y, Kotani T, Ohnishi H, Matozaki T
  • Journal Title: J Biochem
  • DOI: 10.1093/jb/mvu017
  • Peer Reviewed
• [Journal Article] Comprehensive behavioral analysis of cluster of differentiation 47 knockout mice (2014)
  • Author(s): Koshimizu H, Takao K, Matozaki T, Ohnishi H, Miyakawa T
  • Journal Title: PLoSOne Volume: 9 Pages: e89584
  • DOI: 10.1371/journal.pone.0089584
  • Peer Reviewed
• [Journal Article] Signal Regulatory Protein Alpha Is Present in Several Neutrophil Granule Populations and Is Rapidly Mobilized to the Cell Surface to Negatively Fine-Tune Neutrophil Accumulation in Inflammation (2014)
  • Author(s): Stenberg A, Karlsson A, Feuk-Lagerstedt E, Christenson K, Bylund J, Oldenborg A, Vesterlund L, Matozaki T, Sehlin J, Oldenborg PA
  • Journal Title: J Innate Immun
  • DOI: 10.1159/000357820
  • Peer Reviewed
• [Journal Article] Shear Stress-induced Redistribution of Vascular Endothelial-Protein-tyrosine Phosphatase (VE-PTP) in Endothelial Cells and Its Role in Cell Elongation (2014)
  • Author(s): Mantilidewi KI, Murata Y, Mori M, Otsubo C, Kotani T, Kusakari S, Ohnishi H, Matozaki T
  • Journal Title: J Biol Chem Volume: 289 Pages: 6451-61
  • DOI: 10.1074/jbc.M113.529503
  • Peer Reviewed
• [Journal Article] The BALB/c-specific polymorphic SIRPA enhances its affinity for human CD47, inhibiting phagocytosis against human cells to promote xenogeneic engraftment (2014)
  • Author(s): Iwamoto C, Takenaka K, Urata S, Yamauchi T, Shima T, Kuriyama T, Daitoku S, Saito Y, Miyamoto T, Iwasaki H, Kitabayashi I, Itoh K, Kishimoto J, Kohda D, Matozaki T, Akashi K
  • Journal Title: Exp Hematol Volume: 42 Pages: 163-171
  • DOI: 10.1016/j.exphem.2013.11.005
  • Peer Reviewed
• [Journal Article] Autoimmune animal models in the analysis of the CD47-SIRPα signaling pathway (2014)
  • Author(s): Murata Y, Saito Y, Kaneko T, Kotani T, Kaneko Y, Ohnishi H, Matozaki T
  • Journal Title: Methods Volume: 65 Pages: 254-9
  • DOI: 10.1016/j.ymeth.2013.09.016
  • Peer Reviewed
• [Journal Article] Inflammation-induced proteolytic processing of the SIRPα cytoplasmic ITIM in neutrophils propagates a proinflammatory state (2013)
  • Author(s): Zen K, Guo Y, Bian Z, Lv Z, Zhu D, Ohnishi H, Matozaki T, Liu Y
  • Journal Title: Nat Commun Volume: 4 Pages: 2436
  • DOI: 10.1038/ncomms3436
  • Peer Reviewed
• [Journal Article] Lack of CD47 impairs bone cell differentiation and results in an osteopenic phenotype in vivo due to impaired signal regulatory protein α (SIRPα) signaling (2013)
  • Author(s): Koskinen C, Persson E, Baldock P, Stenberg Å, Boström I, Matozaki T, Oldenborg PA, Lundberg P
  • Journal Title: J Biol Chem Volume: 288 Pages: 29333-44
  • DOI: 10.1074/jbc.M113.494591
  • Peer Reviewed
• [Journal Article] SIRPα signaling regulates podocyte structure and function (2013)
  • Author(s): Takahashi S, Tomioka M, Hiromura K, Sakairi T, Hamatani H, Watanabe M, Ikeuchi H, Kaneko Y, Maeshima A, Aoki T, Ohnishi H, Matozaki T, Nojima Y
  • Journal Title: Am J Physiol Renal Physiol Volume: 305 Pages: 861-70
  • DOI: 10.1152/ajprenal.00597.2012
  • Peer Reviewed
• [Journal Article] Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment (2013)
  • Author(s): Yamauchi T, Takenaka K, Urata S, Shima T, Kikushige Y, Tokuyama T, Iwamoto C, Nishihara M, Iwasaki H, Miyamoto T, Honma N, Nakao M, Matozaki T, Akashi K
  • Journal Title: Blood Volume: 121 Pages: 1316-25
  • DOI: 10.1182/blood-2012-06-440354
  • Peer Reviewed
• [Journal Article] Hypothermia-dependent and -independent effects of forced swim on the phosphorylation states of signaling molecules in mouse hippocampus (2012)
  • Author(s): Hayashi Y, Kusakari S, Sato-Hashimoto M, Urano E, Shigeno M, Sekijima T, Kotani T, Murata Y, Murakami H, Matozaki T, Ohnishi H
  • Journal Title: Biochem Biophys Res Commun Volume: 428 Pages: 475-81
  • DOI: 10.1016/j.bbrc.2012.10.083
  • Peer Reviewed
• [Journal Article] The absence of CD47 promotes nerve fiber growth from cultured ventral mesencephalic dopamine neurons (2012)
  • Author(s): Marschinke F, Hashemian S, Matozaki T, Oldenborg PA, Strömberg I
  • Journal Title: PLoSOne Volume: 7 Pages: e45218
  • DOI: 10.1371/journal.pone.0045218
  • Peer Reviewed
• [Journal Article] SIRPα controls the activity of the phagocyte NADPH oxidase by restricting the expression of gp91(phox) (2012)
  • Author(s): van Beek EM, Zarate JA, van Bruggen R, Schornagel K, Tool AT, Matozaki T, Kraal G, Roos D, van den Berg TK
  • Journal Title: Cell Rep Volume: 2 Pages: 748-55
  • DOI: 10.1016/j.celrep.2012.08.027
  • Peer Reviewed
• [Journal Article] Macrophages require Skap2 and Sirpα for integrin-stimulated cytoskeletal rearrangement (2012)
  • Author(s): Alenghat FJ, Baca QJ, Rubin NT, Pao LI, Matozaki T, Lowell CA, Golan DE, Neel BG, Swanson KD
  • Journal Title: J Cell Sci Volume: 125 Pages: 5535-45
  • DOI: 10.1242/jcs.111260
  • Peer Reviewed
• [Journal Article] SHPS-1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress (2012)
  • Author(s): Wang L, Lu Y, Deng S, Zhang Y, Yang L, Guan Y, Matozaki T, Ohnishi H, Jiang H, Li H
  • Journal Title: J Neurochem Volume: 122 Pages: 834-43
  • DOI: 10.1111/j.1471-4159.2012.07818.x
  • Peer Reviewed
• [Journal Article] Dendritic cell-specific ablation of the protein tyrosine phosphatase Shp1 promotes Th1 cell differentiation and induces autoimmunity (2012)
  • Author(s): Kaneko T, Saito Y, Kotani T, Okazawa H, Iwamura H, Sato-Hashimoto M, Kanazawa Y, Takahashi S, Hiromura K, Kusakari S, Kaneko Y, Murata Y, Ohnishi H, Nojima Y, Takagishi K, Matozaki T
  • Journal Title: J Immunol Volume: 188 Pages: 5397-407
  • DOI: 10.4049/jimmunol.1103210
  • Peer Reviewed
• [Journal Article] Hypothermia-induced tyrosine phosphorylation of SIRPα in the brain (2012)
  • Author(s): Maruyama T, Kusakari S, Sato-Hashimoto M, Hayashi Y, Kotani T, Murata Y, Okazawa H, Oldenborg PA, Kishi S, Matozaki T, Ohnishi H
  • Journal Title: J Neurochem Volume: 121 Pages: 891-902
  • DOI: 10.1111/j.1471-4159.2012.07748.x
  • Peer Reviewed
• [Journal Article] The Rho kinase pathway regulates the migration of dendritic cells through SIRP-α (2012)
  • Author(s): Ogura K, Fukunaga A, Taguchi K, Nagai H, Yu X, Oniki S, Okazawa H, Matozaki T, Horikawa T, Nishigori C
  • Journal Title: J Dermatol Sci Volume: 66 Pages: 74-6
  • DOI: 10.1016/j.jdermsci.2012.02.003
  • Peer Reviewed
• [Journal Article] Ohnishi H, Murata Y, Okazawa H, Matozaki T (2011)
  • Author(s): Src family kinases : modulators of neurotransmitter receptor function and behavior
  • Journal Title: Trends Neurosci Volume: 34 Pages: 629-37
  • DOI: 10.1016/j.tins.2011.09.005
  • Peer Reviewed
• [Journal Article] CD47-signal regulatory protein-α (SIRPα) interactions form a barrier for antibody-mediated tumor cell destruction (2011)
  • Author(s): Zhao XW, van Beek EM, Schornagel K, Van der Maaden H, Van Houdt M, Otten MA, Finetti P, Van Egmond M, Matozaki T, Kraal G, Birnbaum D, van Elsas A, Kuijpers TW, Bertucci F, van den Berg TK
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 18342-7
  • DOI: 10.1073/pnas.1106550108
  • Peer Reviewed
• [Journal Article] SIRPα /CD172a regulates eosinophil homeostasis (2011)
  • Author(s): Verjan Garcia N, Umemoto E, Saito Y, Yamasaki M, Hata E, Matozaki T, Murakami M, Jung YJ, Woo SY, Seoh JY, Jang MH, Aozasa K, Miyasaka M
  • Journal Title: J Immunol Volume: 187 Pages: 2268-77
  • DOI: 10.4049/jimmunol.1101008
  • Peer Reviewed
• [Journal Article] Signal regulatory protein α regulates the homeostasis of T lymphocytes in the spleen (2011)
  • Author(s): Sato-Hashimoto M, Saito Y, Ohnishi H, Iwamura H, Kanazawa Y, Kaneko T, Kusakari S, Kotani T, Mori M, Murata Y, Okazawa H, Ware CF, Oldenborg PA, Nojima Y, Matozaki T
  • Journal Title: J Immunol Volume: 187 Pages: 291-7
  • DOI: 10.4049/jimmunol.1100528
  • Peer Reviewed
• [Presentation] 樹状細胞及び二次リンパ組織の恒常性維持におけるSIRPαの役割 (2014)
  • Author(s): 鷲尾健, 小谷武徳, レスパティカダトゥ, 村田陽二, 岡澤秀樹, 大西浩史, 福永淳, 錦織千佳子, 的崎尚
  • Organizer: 第6回日本プロテインホスファターゼ研究会学術集会
  • Place of Presentation: 三重大学(三重)
  • Year and Date: 2014-02-21
• [Presentation] The protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM in the intestinal epithelium FASEB (2013)
  • Author(s): Matozaki T, Murata Y, Kotani T, Yana Supriatna, Okazawa H, Ohnishi H
  • Place of Presentation: The Steamboat Grand(SteamboatSprings/USA)
  • Year and Date: 20130812-13
• [Presentation] SIRPα -CD47 system regulates the homeostasis of dendritic cells in lymphoid tissues (2013)
  • Author(s): Washio K, Kotani T, Datu Respatika, Murata Y, Okazawa H, Ohnishi H, Fukunaga A, Nishigori C, Matozaki T
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2013-12-12
• [Presentation] R3受容体型チロシンホスファターゼの発現, 局在と生理機能 (2013)
  • Author(s): 的崎尚, 村田陽二, 小谷武徳, Yana Supriatna, 森宗昌, 岡澤秀樹, 大西浩史
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場ほか(兵庫)
  • Year and Date: 2013-12-05
• [Presentation] Expression, localization, and biological function of the R3 subtype of receptor-type protein tyrosine phosphatases (2013)
  • Author(s): Matozaki T
  • Organizer: The 2nd Taiwan-Japan Bilateral Conference on Protein Phosphatases
  • Place of Presentation: 国家衛生研究院(新竹市Hsinchu/TAIWAN)
  • Year and Date: 2013-11-29
• [Presentation] 受容体型チロ シンホス フ ァ タ ーゼ SAP-1によ る 腸管免疫制御/Regulation of intestinal immunity by the protein tyrosine phosphatase SAP-1 (2013)
  • Author(s): 村田陽二, 小谷武徳, Supriatna Yana , 森宗昌, 草苅伸也, 岡澤秀樹, 大西浩史, 的崎尚
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2013-10-03
• [Presentation] Role of VE-PTP in shear stress responses of endothelial cells (2013)
  • Author(s): Mantilidewi KI, Murata Y, Mori M, Kotani T, Kusakari S, Okazawa H, Ohnishi H, Matozaki T
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2013-09-11
• [Presentation] Functional Analysis of A non-receptor type protein tyrosine phosphatase Shp2 in the adult brain Neuro2013 (2013)
  • Author(s): Kusakari S, Saitow F, Sato-Hashimoto M, Shibasaki K, Ago Y, Matsuda T, Benjamin G. Neel, Kotani T, Murata Y, Matozaki T, Ohnishi H
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2013-06-20
• [Presentation] Regulation of intestinal immunity by the protein tyrosine phosphatase SAP-1 (2013)
  • Author(s): Murata Y, Kotani T, Yana Supriatna, Daniwijaya EW, Ohnishi H, Matozaki T
  • Organizer: 第10回プロテインホスファターゼ国際カンファレンス
  • Place of Presentation: 国立がん研究センター(東京)
  • Year and Date: 2013-02-08
• [Presentation] 脾臓T細胞の恒常性調節への SIRPα の関与/Signal regulatory protein alpha regulates the homeostasis of T lymphocytes in the spleen (2012)
  • Author(s): 橋本(佐藤)美穂, 齊藤泰之, 金子哲也, 大西浩史, 草苅伸也, 小谷武徳, 村田陽二, 岡澤秀樹, 的崎尚
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場ほか(福岡)
  • Year and Date: 2012-12-16
• [Presentation] 細胞質型チロシンホスファターゼShp2の成熟脳における機能解析/Functional analysis of tyrosine phosphatase Shp2 in the adult brain (2012)
  • Author(s): 草苅伸也, 橋本美穂, 柴崎貢志, 吾郷由希夫, 松田敏夫, Benjamin G. Neel, 小谷武徳, 村田陽二, 的崎尚, 大西浩史
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場ほか(福岡)
  • Year and Date: 2012-12-16
• [Presentation] Protein tyrosine phosphatases and the CD47-SIRPα System that mediates cell-to-cell communication (2012)
  • Author(s): Matozaki T
  • Organizer: The First Taiwan Phosphatase Conference
  • Place of Presentation: 国立成功大学(Tainan/TAIWAN)
  • Year and Date: 2012-11-10
• [Presentation] R egulation of brain functions by a protein tyrosine phosphatase Shp2 (2012)
  • Author(s): Kusakari S, Hashimoto M, Hayashi Y, Kusakari Y, Ago Y, Matsuda T, Shibasaki K, Kotani T, Murata Y, Benjamin G. Neel, Matozaki T, Ohnishi H
  • Organizer: 平成24年度国際シナプス研究会
  • Place of Presentation: 岡崎コンファレンスセンター(愛知)
  • Year and Date: 2012-11-08
• [Presentation] 成熟脳におけるShp2の生理機能解析 (2012)
  • Author(s): 草苅伸也, 小谷武徳, 橋本美穂, 村田陽二, 岡澤秀樹, 吾郷由 紀夫, 松田 敏夫, Benjamin G. Neel, 的崎尚, 大西浩史
  • Organizer: 第5回プロテインホスファターゼ研究会学術集会大阪
  • Place of Presentation: 大阪大学銀杏会館(大阪)
  • Year and Date: 2012-01-19
• [Presentation] 腸微絨毛特異的な発現を示す受容体型チロシンホスファターゼSAP-1による腸管免疫制御 (2012)
  • Author(s): 小谷武徳, 村田陽二, Yana Supriatna, 岡澤秀樹, 大西浩史, Edwin Daniwijaya, 草苅伸也, 定方久延, 大川克也, 的崎尚
  • Organizer: 第5回プロテインホスファターゼ研究会学術集会大阪
  • Place of Presentation: 大阪大学銀杏会館(大阪)
  • Year and Date: 2012-01-19
• [Presentation] The R3 subtype of receptor-type protein tyrosine phosphatases : Expression, localization, and biological function (2011)
  • Author(s): Matozaki T
  • Organizer: The First Japan-Taiwan Bilateral Conference on Protein Phosphatases
  • Place of Presentation: 基礎生物学研究所(愛知)
  • Year and Date: 2011-12-02
• [Presentation] チロシンリン酸化シグナルによるうつ様行動の制御/Regulation by protein tyrosine phosphorylation of depression-like behavior (2011)
  • Author(s): 大西浩史, 的崎尚
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2011-09-17
• [Remarks] 神戸大学大学院医学研究科生化学・分子生物学講座シグナル統合学分野
  • URL: http://www.med.kobe-u.ac.jp/tougou/signal/Home.html