Novel molecular mechanism of neuronal functions by ERK5

• Project/Area Number: 24790063
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Yamagata University
• Principal Investigator: OBARA YUTARO 山形大学, 医学部, 准教授 (40400270)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 神経栄養因子 / NGF / ERK5 / MAPK

Outline of Final Research Achievements

We have indentified many genes regulated by ERK5 selectively. Among them, we focused on p36 and examined its roles. We found that p36 stabilized catecholamine-synthesizing enzyme, tyrosine hydroxylase, and promoted its biosynthesis. Hence, it is assumed that ERK5 and p36 play roles in strength of the neuronal functions during the neuronal differentiation.
In addition, we found that ERK1/2 phosphorylated ERK5 Thr732 and promoted nuclear translocation of ERK5. We could clarify the novel cross-talk mechanism between ERK5 and ERK1/2.

Research Products

• [Journal Article] Phosphorylation of ERK5 on Thr732 is associated with ERK5 nuclear localization and ERK5-dependent transcription. (2015)
  • Author(s): 本多 拓人、小原 祐太郎、山内 新、 Anthony D. Couvillon、 Justin J. Mason、石井 邦明、中畑 則道
  • Journal Title: PLoS ONE Volume: 10 Issue: 2 Pages: e0117914-e0117914
  • DOI: 10.1371/journal.pone.0117914
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Is PIP2 involved in the insulin effect? (2014)
  • Author(s): 石井 邦明、Minghua Wu、小原 祐太郎
  • Journal Title: Channels Volume: 8 Issue: 5 Pages: 391-392
  • DOI: 10.4161/19336950.2014.948758
  • Peer Reviewed
• [Journal Article] Insulin suppresses IKs (KCNQ1/KCNE1) currents, which require β-subunit KCNE1. (2013)
  • Author(s): 呉 明華、小原 祐太郎、野呂田 郁夫、永澤 悦伸、石井 邦明
  • Journal Title: Pflugers Archiv - Eur J Physiol Volume: - Issue: 5 Pages: 937-946
  • DOI: 10.1007/s00424-013-1352-7
  • Peer Reviewed
• [Journal Article] Rap1 regulates actin cytoskeleton at endothelial cell-cell junctions by spatially controlling myosin II activlty (2013)
  • Author(s): Ando K, S. Fukuhara, Y. Obars, T. Noriya. N. Nakahata, N. Moohizuki.
  • Journal Title: Journal of Cell Biology Volume: 202 Issue: 6 Pages: 901-916
  • DOI: 10.1083/jcb.201301115
  • Peer Reviewed
• [Journal Article] Neurite Outgrowth of PC12 Cells by 4'-O-β-D-glucopyranosyl-3',4- dimethoxychalcone from Brassica rapa L. 'hidabeni' was enhanced by pretreatment with p38MAPK inhibitor. (2013)
  • Author(s): 仁科 淳良、Hirokazu Kimura, Hiroyuki Tsukagoshi, Kunihisa Kozawa, Mamoru Koketsu, Masayuki Ninomiya, Daisuke Sato、小原 祐太郎、古川 昭栄
  • Journal Title: Neurochem Res Volume: 38 Issue: 11 Pages: 2397-2407
  • DOI: 10.1007/s11064-013-1152-7
  • Peer Reviewed
• [Journal Article] G_<αh>/transglutaminase-2 activity is required for maximal activatio of adenylylcyclase 8 in human and rat g(n) lioma cells (2013)
  • Author(s): Obara Y, Yanagihata Y, Abe T, Dafik L, Ishii K, Nakahata N.
  • Journal Title: Cell Signal Volume: 25 Issue: 3 Pages: 589-597
  • DOI: 10.1016/j.cellsig.2012.11.021
  • Peer Reviewed
• [Journal Article] ようやく見えて来た神経系におけるERK5の機能 (2013)
  • Author(s): 小原 祐太郎
  • Journal Title: 日本薬理学雑誌 Volume: 141
  • NAID: 10031171126
  • Peer Reviewed
• [Journal Article] 多彩な機能を有するGh/トランスグルタミナーゼ2 (2013)
  • Author(s): 小原 祐太郎、石井 邦明
  • Journal Title: 日本薬理学雑誌 Volume: 141 Pages: 225-225
  • Peer Reviewed
• [Journal Article] 神経系におけるERK5の役割について (2013)
  • Author(s): 小原 祐太郎、石井 邦明
  • Journal Title: 日本薬理学雑誌 Volume: 141
  • NAID: 10031177895
  • Peer Reviewed
• [Journal Article] Endocytic regulation of voltage-dependent potassium channels in heart. (2012)
  • Author(s): 石井 邦明、野呂田 郁夫、小原 祐太郎
  • Journal Title: J. Pharmacol. Sci. Volume: 120 Pages: 264-269
  • NAID: 10031147574
  • Peer Reviewed
• [Journal Article] Involvement of lipid rafts in multiple signal transductions mediated by two isoforms of thromboxane A₂ receptor: Dependency on receptor isoforms and downstream signaling types (2012)
  • Author(s): Shinji Goto, Masaki Saito, Yutaro Obara, Takahiro Moriya, Norimichi Nakahata
  • Journal Title: European Journal of Pharmacology Volume: 693 Issue: 1-3 Pages: 15
  • DOI: 10.1016/j.ejphar.2012.07.046
  • Peer Reviewed
• [Presentation] ERK5 regulates catecholamine biosynthesis and homeostasis in neural cells and human adrenal medullas. (2015)
  • Author(s): 小原 祐太郎、長澤 隆介、根本 亙、Mike J. Pellegrino、高橋 麻穂、Beth A Habecker、Philip J.S Stork、一柳 統、伊藤 裕美、冨田 善彦、石井 邦明、中畑 則道
  • Organizer: 第87回 日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] ERK5とERK1/2のクロストーク機構について (2014)
  • Author(s): 小原 祐太郎、本多 拓人、山内 新、Anthony D. Couvillon、Justin J. Mason、石井 邦明、中畑 則道
  • Organizer: 第65回 日本薬理学会北部会
  • Place of Presentation: コラッセ福島（福島）
  • Year and Date: 2014-09-26 – 2014-09-27
• [Presentation] NGFはRasとRap1非依存的にERK5を活性化し、神経突起の伸展とカテコラミンの生合成を促進する (2014)
  • Author(s): 小原 祐太郎、Philip Stork、Beth Habecker、石井 邦明、中畑 則道
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 仙台国際会議場（仙台）
• [Presentation] ヒトおよびラットグリオーマ細胞において、Gαh/TG2はアデニル酸シクラーゼ8の活性を増大させる (2014)
  • Author(s): 小原 祐太郎、柳畑 佳美、阿部 友大、 Laila Dafik、石井 邦明、中畑 則道
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 仙台国際会議場（仙台）
• [Presentation] Gαh/TG2 promotes cAMP production accompanied by a modification of adenylylcyclase 8 in human and rat glioma cells. (2013)
  • Author(s): 小原 祐太郎、柳畑 佳美、阿部 友大、 Laila Dafik、石井 邦明、中畑 則道
  • Organizer: ニューロサイエンス学会2013
  • Place of Presentation: サンディエゴコンベンションセンター（サンディエゴ、アメリカ）
• [Presentation] 神経栄養因子の作用メカニズムとその生合成機構に関する薬理学的研究 (2013)
  • Author(s): 小原 祐太郎
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Invited
• [Presentation] ERK5とERK1/2のクロストーク機構の解析 (2012)
  • Author(s): 小原 祐太郎、本多 拓人、山内 新、石井 邦明、中畑 則道
  • Organizer: 第63回日本薬理学会北部会
  • Place of Presentation: 朱鷺メッセ（新潟）