Comprehensive identification and signal transduction analysis of calmodulin-targets by functional proteomics

• Project/Area Number: 21570143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kagawa University
• Principal Investigator: TOKUMITSU Hiroshi 香川大学, 医学部, 准教授 (20237077)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Ryouji 香川大学, 医学部, 教授 (00020917)
• Co-Investigator(Renkei-kenkyūsha): HATANO Naoya 神戸大学, 医学(系)研究科, 研究員 (10332280)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: Wolframin / PRG-1 / カルモデュリン / 機能プロテオミクス / GST / LC-MS/ MS / CaMKK / タンパク質リン酸化反 / Syndapin I / ATPアナログ / 変異体 / 自己リン酸化 / LC-MS/MS / Calmodulin / シナプス / カルシウム情報伝達 / 樹状突起 / 海馬 / WFS1 / LC-MS / MS / Wolframin症候群

Research Abstract

We have identified Wolframin and PRG-1 from rat brain as novel calmodulin binding proteins by functional proteomics using calmodulin-GST fused protein and LC-MS/ MS technique. According to the biochemical study, we have demonstrated that some mutations causing Wolfram syndrome disrupt calmodulin-binding ability of wolframin.

Research Products

• [Journal Article] S100 proteins modulate protein phosphatase 5 function : a link between Ca^<2+> signal transduction and protein dephosphorylation (2012)
  • Author(s): Yamaguchi F, Umeda Y, Shimamoto S, Tsuchiya M, Tokumitsu H, Tokuda M, and Kobayahsi R
  • Journal Title: J. Biol. Chem Volume: (掲載確定)
• [Journal Article] Exendin-4 regulates GLUT2 expression via the CaMKK/ CaMKIV pathway in a pancreatic beta-cell line (2011)
  • Author(s): Chen K, Yu X, Murao K, Imachi H, Li J, Muraoka T, Masugata H, Zhang GX, Kobayashi R, Ishida T, and Tokumitsu H
  • Journal Title: Metabolism Volume: 60 Pages: 579-585
• [Journal Article] Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium (2011)
  • Author(s): El-Hashash AH, Turcatel G, Al Alam D, Buckley S, Tokumitsu H, Bellusci S, and Warburton D
  • Journal Title: Development Volume: 138 Pages: 1395-1407
• [Journal Article] Identification of a novel CaMKK substrate (2011)
  • Author(s): Fujimoto T, Hatano N, Nozaki N, Yurimoto S, Kobayashi R, and Tokumitsu H
  • Journal Title: Biochem. Biophys. Res. Comm Volume: 410 Pages: 45-51
• [Journal Article] Local application of neurotrophins specifies axons through inositol 1, 4, 5-trisphosphate, calcium, and Ca^<2+>/ calmodulin. dependent protein kinases (2011)
  • Author(s): Nakamuta S, Funahashi Y, Namba T, Arimura N, Picciotto MR, Tokumitsu H, Soderling TR, Sakakibara A, Miyata T, Kamiguchi H, and Kaibuchi K
  • Journal Title: Sci. Signal Volume: 4
• [Journal Article] Generation of Autonomous Activity of Ca^<2+>/ Calmodulin-Dependent Protein Kinase Kinaseβby Autophosphorylation (2011)
  • Author(s): Tokumitsu H, Hatano N, Fujimoto T, Yurimoto S, and Kobayashi R
  • Journal Title: Biochemistry Volume: 50 Pages: 8193-8201
• [Journal Article] Analysis of CaM-kinase Signaling in Cells (2011)
  • Author(s): Wayman GA, Tokumitsu H, Davare MA, and Soderling TR
  • Journal Title: Cell Calcium Volume: 50 Pages: 1-8
• [Journal Article] Generation of Autonomous Activity of Ca^<2+>/Calmodulin-Dependent Protein Kinase Kinase β by Autophosphorylation (2011)
  • Author(s): Tokumitsu H, et al
  • Journal Title: Biochemistry Volume: 50 Issue: 38 Pages: 8193-8201
  • DOI: 10.1021/bi201005g
  • Peer Reviewed
• [Journal Article] Local Application of Neurotrophins Specifies Axons Through Inositol 1,4,5-Trisphosphate, Calcium, and Ca^,<2+>/Calmodulin-Dependent Protein Kinases (2011)
  • Author(s): Nakamuta S., et al
  • Journal Title: Science Signaling Volume: 4 Issue: 199
  • DOI: 10.1126/scisignal.2002011
  • Peer Reviewed
• [Journal Article] Identification of a novel CaMKK substrate (2011)
  • Author(s): Tomohito Fujimoto, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 410 Issue: 1 Pages: 45-51
  • DOI: 10.1016/j.bbrc.2011.05.102
  • Peer Reviewed
• [Journal Article] Eyal controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium (2011)
  • Author(s): El-Hashash AH, et al
  • Journal Title: Development Volume: 138 Issue: 7 Pages: 1395-1407
  • DOI: 10.1242/dev.058479
  • Peer Reviewed
• [Journal Article] Exendin-4 regulates GLUT2 expression via the CaMKK/CaMKIV pathway in a pancreatic beta-cell line (2011)
  • Author(s): Chen K, et al
  • Journal Title: Metabolism Volume: 60 Issue: 4 Pages: 579-585
  • DOI: 10.1016/j.metabol.2010.06.002
  • Peer Reviewed
• [Journal Article] Exendin-4 regulates GLUT2 expression via the CaMKK/CaMKIV pathway in a pancreatic beta-cell line. (2011)
  • Author(s): Chen, et al.
  • Journal Title: Metabolism Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Analysis of CaM-kinase Signaling in Cells. (2011)
  • Author(s): Wayman, et al.
  • Journal Title: Cell Calcium Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Exendin-4 regulates pancreatic ABCA1 transcription via CaMKK/ CaMKIV pathway (2010)
  • Author(s): Li J, Murao K, Imachi H, Masugata H, Iwama H, Tada S, Zhang GX, Kobayashi R, Ishida T, and Tokumitsu H
  • Journal Title: J. Cell. Mol. Med Volume: 14 Pages: 1083-1087
• [Journal Article] S100 proteins regulate the interaction of Hsp90 with Cyclophilin 40 and FKBP52 through their tetratricopeptide repeats (2010)
  • Author(s): Shimamoto S, Kubota Y, Tokumitsu H, and Kobayashi R
  • Journal Title: FEBS Lett Volume: 584 Pages: 1119-1125
• [Journal Article] Inactivation of Ca^<2+>/ calmodulin-dependent protein kinase I by S-glutathionylation of the active-site cysteine residue (2010)
  • Author(s): Kambe T, Song T, Takata T, Hatano N, Miyamoto Y, Nozaki N, Naito Y, Tokumitsu H, and Watanabe Y
  • Journal Title: FEBS Lett Volume: 584 Pages: 2478-2484
• [Journal Article] Identification and characterization of PRG-1 as a neuronal calmodulin-binding protein (2010)
  • Author(s): Yurimoto S, Fujimoto T, Ohara N, Kobayashi R, and Sakagami H
  • Journal Title: Biochem. J Volume: 431 Pages: 81-91
• [Journal Article] Regulation of nuclear localization signal-importin・interaction by Ca^<2+>/ S100A6 (2010)
  • Author(s): Takata M, Shimamoto S, Yamaguchi F, Tokuda M, Tokumitsu H, and Kobayashi R
  • Journal Title: FEBS Lett Volume: 584 Pages: 4517-4523
• [Journal Article] Identification and characterization of PRG-1 as a neuronal calmodulin-binding protein. (2010)
  • Author(s): Tokumitsu, et al.
  • Journal Title: Biochemical Journal Volume: 431 Pages: 81-91
  • Peer Reviewed
• [Journal Article] Regulation of nuclear localization signal-importin a interaction by Ca^<2+>/S100A6. (2010)
  • Author(s): Takata, et al.
  • Journal Title: FEBS Letters Volume: 584 Pages: 4517-4523
  • Peer Reviewed
• [Journal Article] Inactivation of Ca^<2+>/calmodulin-dependent protein kinase I by S-glutathionylation of the active-site cysteine residue. (2010)
  • Author(s): Kambe, et al.
  • Journal Title: FEBS Letters Volume: 584 Pages: 2478-2484
  • Peer Reviewed
• [Journal Article] Exendin-4 regulates pancreatic ABCA1 transcription via CaMKK/CaMKIV pathway (2010)
  • Author(s): Li, et al.
  • Journal Title: Journal of Cellular and Molecular Medicine (印刷中)
  • Peer Reviewed
• [Journal Article] S100 proteins regulate the interaction of Hsp90 with FKBP52 and Cyclophilin 40 through their tetratricopeptide repeats (2010)
  • Author(s): Shimamoto, et al.
  • Journal Title: FEBS Letters (印刷中)
  • Peer Reviewed
• [Journal Article] Breast cancer cells expressing stem cell markers CD44+ CD24 lo are eliminated by Numb-1 peptide-activated T cells (2009)
  • Author(s): Mine T, Matsueda S, Li Y, Tokumitsu H, Gao H, Danes C, Wong KK, Wang X, Ferrone S, and Ioannides CG
  • Journal Title: Cancer Immunol. Immunother Volume: 58 Pages: 1185-1194
• [Journal Article] Identification and characterization of wolframin, the product of the wolfram syndrome gene(WFS1), as a novel calmodulin-binding protein (2009)
  • Author(s): Yurimoto S, Hatano N, Tsuchiya M, Kato K, Fujimoto T, Masaki T, Kobayashi R, and Tokumitsu H
  • Journal Title: Biochemistry Volume: 48 Pages: 3946-3955
• [Journal Article] Exendin-4 regulates glucokinase expression by CaMKK/ CaMKIV pathway in pancreatic beta-cell line (2009)
  • Author(s): Murao K, Li J, Imachi H, Muraoka T, Masugata H, Zhang GX, Kobayashi R, Ishida T, and Tokumitsu H
  • Journal Title: Diabetes Obes. Metab Volume: 11 Pages: 939-946
• [Journal Article] Identification and Characterization of Wolframin, the Product of the Wolfram Syndrome Gene (WFS1), as a Novel Calmodulin-Binding Protein (2009)
  • Author(s): Yurimoto, et al.
  • Journal Title: Biochemistry 48 Pages: 3946-3955
  • Peer Reviewed
• [Journal Article] Breast cancer cells with stem cell-type markers (CD44+ CD24lo) are eliminated by Notch and Numb peptide -activated T cells (2009)
  • Author(s): Mine, et al.
  • Journal Title: Cancer Immunology Immunotherapy 58 Pages: 1185-1194
  • Peer Reviewed
• [Journal Article] Exendin-4 regulates Glucokinase expression via CaMKK/CaMKIV pathway in pancreatic β cell line (2009)
  • Author(s): Murao, et al.
  • Journal Title: Diabetes, Obesity and Metabolism 11 Pages: 939-946
  • Peer Reviewed
• [Presentation] Identification of a novel target for Ca^<2+>/ CaM-dependent protein kinase kinase by using an ATP analogue (2011)
  • Author(s): 藤本智仁, 波多野直哉, 野崎直仁, 横倉(揺本)沙紀, 小林良二, 徳光浩
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] Regulatory Mechanism of CaMKK by Autophosphorylation (2011)
  • Author(s): 徳光浩、横倉(揺本)沙紀、波多野直哉、藤本智仁、小林良二
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] Identification of a novel target for Ca^<2+>/CaM-dependent protein kinase kinase by using an ATP analogue (2011)
  • Author(s): 藤本智仁
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] Ca^<2+>/ calmodulin-dependent protein kinae kinase ca utilize GTP as a phosphate donor (2010)
  • Author(s): 藤本智仁、小林良二、徳光浩
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会,合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] S100タンパク質はCHIP(E3)を介したユビキチン化を制御する (2010)
  • Author(s): 嶋本聖子、小林良二
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会,合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] PRG-1(plasticity related gene 1), a novel neuronal calmodulin-binding protein (2010)
  • Author(s): 徳光浩、波多野直哉、土屋光正、横倉(揺本)沙紀、藤本智仁、小原直樹、小林良二、阪上洋行
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会,合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] PRG-1 (plasticity related gene 1), a novel neuronal calmodulin-binding protein (2010)
  • Author(s): Tokumitsu, et al.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-09
• [Presentation] Ca^<2+>/calmodulin-dependent protein kinase kinase can utilize GTP as a phosphate donor (2010)
  • Author(s): Fujimoto, et al.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-09
• [Presentation] 新規カルモデュリン結合タンパク質、PRG-1の同定と生化学的解析 (2009)
  • Author(s): 土屋光正, 他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Ca/S100タンパク質によるユビキチンリガーゼCHIPの活性制御 (2009)
  • Author(s): 嶋本聖子, 他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23