Identification of kinase substrates by using radioactive ATP and LC-Maldi-MS/MS

2010 Fiscal Year Final Research Report

• Project/Area Number: 20510191
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied genomics
• Research Institution: Kumamoto University
• Principal Investigator: IRIE Atsushi Kumamoto University, 大学院・生命科学研究部, 講師 (30250343)
• Co-Investigator(Renkei-kenkyūsha): ARAKI Norie 熊本大学, 大学院・生命科学研究部, 准教授 (80253722)
• Project Period (FY): 2008 – 2010
• Keywords: プロテオーム / シグナル伝達 / 質量分析 / 放射性同位元素 / 免疫細胞

Research Abstract

PKD2 is a major subtype of the PKD family kinases expressed in T cells. We found that one of the substrates of PKD2 is SET protein, a natural inhibitor of PP2A phosphatase. One of the phosphorylation site in SET protein by PKD2 is revealed to be Ser171 and the phosphorylation compromised the inhibitory effect of SET protein to PP2A. In addition, knockdown of PKD2 expression in Jurkat cells suppressed up-regulation of PP2A activity after TCR stimulation.

Research Products

• [Journal Article] Degradation of fibrinogen and collagen by staphopains, cysteine proteases released from Staphylococcus aureus. (2011)
  • Author(s): Ohbayashi T, Irie A, Murakami Y, Nowak M, Potempa J, Nishimura Y, Shinohara M, Imamura T
  • Journal Title: Microbiology 157 Pages: 786-792
  • Peer Reviewed
• [Journal Article] Identification of HLA-A2-restricted CTL epitopes of a novel tumor-associated antigen, KIF20A, overexpressed in pancreatic cancer. (2011)
  • Author(s): Imai K, Hirata S, Irie A, Senju S, Ikuta Y, Yokomine K, Harao M, Inoue M, Tomita Y, Tsunoda T, Nakagawa H, Nakamura Y, Baba H, Nishimura Y
  • Journal Title: Brit.J.Cancer 104 Pages: 300-307
  • Peer Reviewed
• [Journal Article] Peptides derived from human insulin-like growth factor (IGF)-II mRNA binding protein 3 can induce human leukocyte antigen-A2-restricted cytotoxic T lymphocytes reactive to cancer cells. (2011)
  • Author(s): Tomita Y, Harao M, Senju S, Imai K, Hirata S, Irie A, Inoue M, Hayashida Y, Yoshimoto K, Shiraishi K, Mori T, Nomori H, Kohrogi H, Nishimura Y
  • Journal Title: Cancer Science 102 Pages: 71-78
  • Peer Reviewed
• [Journal Article] Identification of SPARC as a candidate target antigen for immunotherapy of various cancers. (2010)
  • Author(s): Inoue M, Senju S, Hirata S, Ikuta Y, Hayashida Y, Irie A, Harao M, Imai K, Tomita Y, Tsunoda T, Furukawa Y, Ito T, Nakamura Y, Baba H, Nishimura Y
  • Journal Title: Int.J.Cancer 127 Pages: 1393-1403
  • Peer Reviewed
• [Journal Article] Identification of SARS-CoV spike protein-derived and HLA-A2-restricted human CTL epitopes by using a new muramyl dipeptidederivative adjuvant. (2010)
  • Author(s): Chen YZ, Liu G, Senju S, Wang Q, Irie A, Haruta M, Matsui M, Yasui F, Kohara M, Nishimura Y
  • Journal Title: Int J Immunopathol Pharmacol. 23 Pages: 165-177
  • Peer Reviewed
• [Journal Article] The forkhead box M1 transcription factor as a candidate of target for anti-cancer immunotherapy. (2010)
  • Author(s): Yokomine K, Senju S, Nakatsura T, Irie A, Hayashida Y, Ikuta Y, Harao M, Imai K, Baba H, Iwase H, Nomori H, Takahashi K, Daigo Y, Tsunoda T, Nakamura Y, Sasaki Y, Nishimura Y
  • Journal Title: Int.J.Cancer 126 Pages: 2153-2163
  • Peer Reviewed
• [Journal Article] An in vivo model of priming of antigen-specific human CTL by Mo-DC in NOD/Shi-scid IL2rg^<null> (NOG) mice. (2010)
  • Author(s): Inoue M, Senju S, Hirata S, Irie A, Baba H, Nishimura Y
  • Journal Title: Immunol.Lett. 126 Pages: 67-72
  • Peer Reviewed
• [Journal Article] Pro- and anti-apoptotic dual functions of the C5a receptor : involvement of regulator of G protein signaling 3 and extracellular signal-regulated kinase. (2009)
  • Author(s): Nishiura H, Nonaka H, Revollo IS, Semba U, Li Y, Ota Y, Irie A, Harada K, Kehrl JH, Yamamoto T
  • Journal Title: Lab.Invest. 89 Pages: 676-694
  • Peer Reviewed
• [Journal Article] Identification of the H2-Kd-restricted cytotoxic T lymphocyte epitopes of a tumor-associated antigen, SPARC, which can stimulate antitumor immunity without causing autoimmune disease in mice. (2009)
  • Author(s): Ikuta Y, Hayashida Y, Hirata S, Irie A, Senju S, Kubo T, Nakatsura T, Monji M, Sasaki Y, Baba H, Nishimura Y
  • Journal Title: Cancer Sci. 100 Pages: 132-137
  • Peer Reviewed
• [Journal Article] An integrated approach of differential mass spectrometry and gene ontology analysis identified novel proteins regulating neuronal differentiation and survival. (2009)
  • Author(s): Kobayashi D, Kumagai J, Morikawa T, Wilson-Morifuji M, Wilson A, Irie A, Araki N
  • Journal Title: Mol.Cell Proteomics 8 Pages: 2350-2367
  • Peer Reviewed
• [Journal Article] Production of C5a by ASP, a serine protease released from Aeromonas sobria. (2008)
  • Author(s): Nitta H, Imamura T, Wada Y, Irie A, Kobayashi H, Okamoto K, Baba H
  • Journal Title: J.Immunol. 181 Pages: 3602-3608
  • Peer Reviewed
• [Journal Article] HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL. (2008)
  • Author(s): Harao M, Hirata S, Irie A, Senju S, Nakatsura T, Komori H, Ikuta Y, Yokomine K, Imai K, Inoue M, Harada K, Mori T, Tsunoda T, Nakatsuru S, Daigo Y, Nomori H, Nakamura Y, Baba H, Nishimura Y
  • Journal Title: Int.J.Cancer 123 Pages: 2616-2625
  • Peer Reviewed
• [Journal Article] Identification of a novel tumor-associated antigen, cadherin 3/P-cadherin, as a possible target for immunotherapy of pancreatic, gastric, and colorectal cancers. (2008)
  • Author(s): Imai K, Hirata S, Irie A, Senju S, Ikuta Y, Yokomine K, Harao M, Inoue M, Tsunoda T, Nakatsuru S, Nakagawa H, Nakamura Y, Baba H, Nishimura Y
  • Journal Title: Clin.Cancer Res. 14 Pages: 6487-6495
  • Peer Reviewed
• [Journal Article] NF1 tumor suppressor, neurofibromin, regulates the neuronal differentiation of PC12 cells via its associating protein, collapsin response mediator protein-2. (2008)
  • Author(s): Patrakitkomjorn S, Kobayashi D, Morikawa T, Wilson-Morifuji M, Tsubota N, Irie A, Ozawa T, Aoki M, Arimura N, Kaibuchi K, Saya H, Araki N
  • Journal Title: J.Biol.Chem. 283 Pages: 9399-9413
  • Peer Reviewed
• [Journal Article] B-Raf-mediated signaling pathway regulates T cell development. (2008)
  • Author(s): Tsukamoto H, Irie A, Senju S, Hatzopoulos AK, Wojnowski L, Nishimura Y
  • Journal Title: Eur.J.Immunol. 38 Pages: 518-527
  • Peer Reviewed
• [Presentation] Protein kinase D2 regulates protein phosphatase 2A (PP2A) activity through phosphorylation of Ser171 of a PP2A inhibitor, SET, in human T cells. (2010)
  • Author(s): 入江厚, 原田久美子, 荒木令江, 西村泰治
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸、神戸国際会議場、神戸ポートピアホテル
  • Year and Date: 20100823-20100827
• [Presentation] Identification of HLA-A24-restricted CTL epitopes of SARS-CoV protein. (2009)
  • Author(s): Chen YZ, Liu G, Senju S, Qidi W, Irie A, Haruta M, Matsui M, Nishimura Y
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 20091202-20091204
• [Presentation] Protein kinase D2 regulatesprotein phosphatase 2A (PP2A) activity through phosphorylation ofSer171 of a PP2A inhibitor, SET, in human T cells. (2009)
  • Author(s): Irie A, Harada K, Nishimura Y
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 20091202-20091204
• [Presentation] プロテインキナーゼD2によるSETのリン酸化を介したPP2Aの活性制御 (2009)
  • Author(s): 入江厚、原田久美子、西村泰治
  • Organizer: 第4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: 熊本、熊本大学
  • Year and Date: 20091113-20091114
• [Presentation] ヒトdiffuse-type胃癌に高発現するSPARCを標的としたマウス癌免疫療法モデルの構築 (2009)
  • Author(s): 林田裕希、生田義明、平田真哉、入江厚、千住覚、横峰和典、池田徳典、井上光弘、中面哲也、片桐豊雅、古川洋一、角田卓也、馬場秀夫、中村祐輔、佐々木裕、西村泰治
  • Organizer: 第13回日本がん免疫学会
  • Place of Presentation: 小倉、北九州国際会議場
  • Year and Date: 20090624-20090625
• [Presentation] 肺癌の免疫療法に有用な新規癌関連抗原、CDC45Lの同定 (2009)
  • Author(s): 冨田雄介、今井克憲、入江厚、池田徳典、平田真哉、原尾美智子、井上光弘、角田卓也、森毅、千住覚、中村祐輔、伊藤隆明、野守裕明、興梠博次、西村泰治
  • Organizer: 第13回日本がん免疫学会
  • Place of Presentation: 小倉、北九州国際会議場
  • Year and Date: 20090624-20090625
• [Presentation] S-Guanylation proteomics : unique post-translational modification of thiols dependent on nitric oxide and reactive oxygen species. (2009)
  • Author(s): 澤智裕、藤井重元、入江厚、岡本竜哉、居原秀、本橋ほづみ、山本雅之、赤池孝章
  • Organizer: 第9回日本NO学会学術集会
  • Place of Presentation: 静岡、グランシップ
  • Year and Date: 20090508-20090509
• [Presentation] PKD2によるSET-Ser171のリン酸化はPP2Aホスファターゼ活性を制御する (2008)
  • Author(s): 入江厚、原田久美子、荒木令江、西村泰治
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都、京都国際会館
  • Year and Date: 20081201-20081203
• [Presentation] NO dependent modification of Keapl thiol by nitrated nucleotide, 8-nitroguanosine 3', 5' -cyclic monophosphate. (2008)
  • Author(s): Sawa T, Fujii S, Irie A, Okamoto T, Kobayashi A, Yamamoto M, Akaike T
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 20081028-20081030
• [Presentation] Nitric oxide-dependent sulfhydryl modification of Keapl by 8-nitroguanosine 3', 5' -cyclic monophosphate. (2008)
  • Author(s): Sawa T, Fujii S, Irie A, Okamoto T, Motohashi H, Yamamoto M, Akaike T
  • Organizer: 5th International Conference on Biology, Chemistry and Therapeutic applications of NO
  • Place of Presentation: Bregenz, (Festspielhaus Bregenz), Austria
  • Year and Date: 20080824-20080828
• [Presentation] PKD2によるSET-Ser171のリン酸化はPP2Aホスファターゼ活性を制御する (2008)
  • Author(s): 入江厚、原田久美子、荒木令江、西村泰治
  • Organizer: 第6回日本ヒトプロテオーム機構大会
  • Place of Presentation: 大阪、ホテル阪急エキスポパーク
  • Year and Date: 20080729-20080730
• [Presentation] T細胞免疫応答に関わるプロテインキナーゼD2の解析 (2008)
  • Author(s): 入江厚
  • Organizer: 第5回プロテオミクスシンポジウム
  • Place of Presentation: 熊本、熊本大学
  • Year and Date: 2008-03-11
• [Book] Janeway's免疫生物学(Janeway's Immunobiology, 7th ed.)(「第5章T細胞に対する抗原提示」の翻訳) (2010)
  • Author(s): 西村泰治、入江厚
  • Total Pages: 181-217
  • Publisher: 南江堂
• [Book] エッセンシャル免疫学(第2版)(原著The Immune System, 3rd ed.)(「第16章がんと免疫系の相互作用」の翻訳) (2010)
  • Author(s): 入江厚、西村泰治
  • Total Pages: 480-497
  • Publisher: メディカルサイエンスインターナショナル
• [Book] 免疫学最新イラストレイテッド(改訂第2版)(「第12 章移植免疫」)(小安重夫編) (2009)
  • Author(s): 西村泰治、入江厚、千住覚
  • Total Pages: 257-286
  • Publisher: 羊土社
• [Book] インテグリンファミリー(広範囲血液・尿化学検査免疫学的検査-その数値をどう読むか-日本臨床、68巻)
  • Author(s): 入江厚
  • Publisher: 日本臨床社
• [Remarks] ホームページ等
  • URL: http://www.medic.kumamoto-u.ac.jp/dept/immunoge/immunoge.html