Novel neural targets of the Rap2-MAP4K signaling

• Project/Area Number: 20590311
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: University of the Ryukyus
• Principal Investigator: KARIYA Ken-ichi University of the Ryukyus, 大学院・医学研究科, 教授 (40263371)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: MAP4K / Rap2 / 神経系

Research Abstract

We found previously that small G protein Rap2 activates MAP4Ks (NIK and TNIK) placed upstream of JNK. This Rap2-MAP4K system was confirmed by others in neurons and used to explain LTD. In this study, we identified the third MAP4K (MINK) for this system and its phosphorylation target, a PSD protein TANC1. We have also shown that Rap2 localizes to the recycling endosome, the source of glutamate receptors mobilized during LTP. In addition, a mechanism for regulation of neural Rap2-MAP4K system by Rap2 ubiquitination has been revealed.

Research Products

• [Journal Article] The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function. (2011)
  • Author(s): Wang, Q., et al.
  • Journal Title: Mol Psychiatry Volume: (in press)
  • Peer Reviewed
• [Journal Article] Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. (2010)
  • Author(s): Kawabe, H., Neeb, A., Dimova, K., Young, S.M. Jr., Takeda, M., Katsurabayashi, S., Mitkovski, M., Malakhova, O.A., Zhang, D.E., Umikawa, M., Kariya, K., Goebbels, S., Nave, K.A., Rosenmund, C., Jahn, O., Rhee, J., Brose, N.
  • Journal Title: Neuron. 65 Pages: 358-372
  • Peer Reviewed
• [Journal Article] Ectopic coexpression of keratin 8 and 18 promotes invasion of transformed keratinocytes and is induced in patients with cutaneous squamous cell carcinoma. (2010)
  • Author(s): Yamashiro, Y., Takei, K., Umikawa, M., Asato, T., Oshiro, M., Uechi, Y., Ishikawa, T., Taira, K., Uezato, H., Kariya, K.
  • Journal Title: Biochem. Biophys.Res.Commun. 399 Pages: 365-372
  • Peer Reviewed
• [Journal Article] Impact of human papillomavirus genotype on response to treatment and survical in patients receiving radiotherapy for squamous cell carcioma of the cervix. (2010)
  • Author(s): Ferdousi, J., Nagai, Y., Asato, T., Hirakawa, M., Inamine, M., Kudaka, W., Kariya, K., Aoki, Y.
  • Journal Title: Exp.Therap.Med. 1 Pages: 525-530
  • Peer Reviewed
• [Journal Article] Ectopic coexpression of keratin 8 and 18 promotes invasion of transformed keratinocytes and is induced in patients with cutaneous squamous cell carcinoma. (2010)
  • Author(s): Yamashiro, Y., et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 399 Pages: 365-372
  • Peer Reviewed
• [Journal Article] Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. (2010)
  • Author(s): Kawabe, H., et al.
  • Journal Title: Neuron Volume: 65 Pages: 358-372
  • Peer Reviewed
• [Journal Article] Caenorhabditis elegans FOS-1 and JUN-1 regulate plc-1 expression in the spermatheca to control ovulation. (2009)
  • Author(s): Hiatt, S.M., Duren, H.M., Shyu, Y.J., Ellis, R.E., Hisamoto, N., Matsumoto, K., Kariya, K., Kerppola, T.K., Hu, C.D.
  • Journal Title: Mol.Biol.Cell. 20 Pages: 3888-3895
  • Peer Reviewed
• [Journal Article] Rap2 function requires palmitoylation and recycling endosome localization. (2009)
  • Author(s): Uechi, Y., Bayarjargal, M., Umikawa, M., Oshiro, M., Takei, K., Yamashiro, Y., Asato, T., Endo, S., Misaki, R., Taguchi, T., Kariya, K.
  • Journal Title: Biochem. Biophys.Res.Commun. 378 Pages: 732-737
  • Peer Reviewed
• [Journal Article] Rap2 function requires palmitoylation and recycling endosome localization. (2009)
  • Author(s): Uechi Y, et al
  • Journal Title: Biochemical and Biophysical Research Communications 378 Pages: 732-737
  • Peer Reviewed
• [Journal Article] MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold protein TANC1. (2008)
  • Author(s): Nonaka, H., Takei, K., Umikawa, M., Oshiro, M., Kuninaka, K., Bayarjargal, M., Asato, T., Yamashiro, Y., Uechi, Y., Endo, S., Suzuki, T., Kariya, K.
  • Journal Title: Biochem. Biophys.Res.Commun. 377 Pages: 573-578
  • Peer Reviewed
• [Journal Article] Proteomic analysis of rat retina in a steroid-induced ocular hypertension model : potential vulnerability to oxidative stress. (2008)
  • Author(s): Miyara, N., Shinzato, M., Yamashiro, Y., Iwamatsu, A., Kariya, K., Sawaguchi, S.
  • Journal Title: Jpn.J.Ophthalmol. 52 Pages: 84-90
  • NAID: 10024153683
  • Peer Reviewed
• [Journal Article] MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold protein TANC1. (2008)
  • Author(s): Nonaka H, et al
  • Journal Title: Biochemical and Biophysical Research Communications 377 Pages: 573-578
  • Peer Reviewed
• [Presentation] The proteomic search for prognosis markers of cutaneous squamous cell carcinoma. : MBSJ2009 (2009)
  • Author(s): Yoshito Yamashiro(代表発表者), Kimiko Takei, Masato Umikawa, Tsuyoshi Asato, Kiyohito Taira, Hiroshi Uezato, Ken-ichi Kariya
  • Organizer: (第32回日本分子生物学会年会)プログラム:3P-0743 : 418
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-11
• [Presentation] Localization of Rap2 in recycling endosome in a palmitoylationdependent manner. : Biochemistry Molecular Biology (BMB) 2008 (2008)
  • Author(s): Maitsetseg Bayarjargal(代表発表者), Yukiko Uechi, Shogo Endo, Kimiko Nonaka-Takei, Minoru Oshiro, Masato Umikawa, Tsuyoshi Asato, Yoshito Yamashiro, Tomohiko Taguchi, Ken-ichi Kariya
  • 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)プログラム:1P-0444 : 219
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2008-12-09
• [Presentation] Localization of Rap2 in recycling endosome in a palmitoylation-dependent manner. (2008)
  • Author(s): Bayarjargal M, et al
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 兵庫県、神戸国際展示場
  • Year and Date: 2008-12-09