Functions of protein kinases in tumorigenesis

2009 Fiscal Year Final Research Report

• Project/Area Number: 17014012
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: GOTOH Yukiko The University of Tokyo, 分子細胞生物学研究所, 教授 (70252525)
• Project Period (FY): 2005 – 2009
• Keywords: Akt / がん遺伝子 / Mdm2 / 細胞運動

Research Abstract

The proto-oncogene Akt is a key regulator of various biological processes such as cell proliferation, survival, metabolism and motility, as well as tumorigenesis. We have shown that the serine/threonine kinase PAK serves as a scaffold protein in the Akt signaling pathway. We also found that inactivation of PAK1 reduced phosphorylation of only a subset of Akt substrates and suppressed Akt-mediated cell motility but not cell survival or protein synthesis. PAK thus appears to contribute to the signaling specificity of Akt, in addition to its signaling efficiency. PAK appears to affect the signaling specificity of Akt by regulating subcellular localization of a specific isoform of Akt as well as by associating with a subset of Akt substrates related to cell motility regulation. We are now further examining the mechanism by which Akt regulates cell motility.

Research Products

• [Journal Article] Wnt signaling and its downstream target N-Myc regulate basal progenitors in the developing neocortex. (2010)
  • Author(s): Kuwahara, A., Hirabayashi, Y., Knoepfler, P.S., Taketo, M.M., Sakai, J., Kodama, T., Gotoh, Y.
  • Journal Title: Development 137(7) Pages: 035-44
  • Peer Reviewed
• [Journal Article] Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition. (2009)
  • Author(s): Hirabayashi, Y., Suzki, N., Tsuboi, M., Endo, T.A., Toyoda, T., Shinga, J., Koseki, H., Vidal, M., Gotoh, Y.
  • Journal Title: Neuron 63 Pages: 600-613
  • Peer Reviewed
• [Journal Article] Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1. (2009)
  • Author(s): Oishi, K., Watatani, K., Itoh, Y., Okano, H., Guillemot, F., Nakajima, K., Gotoh, Y.
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 3064-13069
  • Peer Reviewed
• [Journal Article] Scaffolding function of PAK in the PDK1-Akt pathway. (2008)
  • Author(s): Higuchi, M., Onishi, K., Yoneyama, C., Gotoh, Y.
  • Journal Title: Nat. Cell Biol. 10 Pages: 1356-1364
  • Peer Reviewed
• [Journal Article] Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse telencephalon. (2008)
  • Author(s): Kawaguchi, D., Yoshimatsu, T., Hozumi, K., Gotoh, Y.
  • Journal Title: Development 135 Pages: 3849-3858
  • Peer Reviewed
• [Journal Article] JNK phosphorylates Syt 4 and enhances Ca2+-evoked release. (2008)
  • Author(s): Mori, Y., Higuchi, M., Hirabayashi, Y., Fukuda, M., Gotoh, Y.
  • Journal Title: EMBO J. 27 Pages: 76-87
  • Peer Reviewed
• [Journal Article] The cdk inhibitors p57 and p27 regulate neuronal migration in the developing mouse neocortex. (2007)
  • Author(s): Itoh, Y., Masuyama, N., Nakayama, K., Nakayama, K.I., Gotoh, Y.
  • Journal Title: J. Biol. Chem. 282 Pages: 390-396
  • Peer Reviewed
• [Journal Article] he PI3K-Akt pathway promotes microtubule stabilization in migrating fibroblasts. (2007)
  • Author(s): Onishi, K., Higuchi, M., Asakura, T., Masuyama, N.,, Gotoh, Y.
  • Journal Title: Genes to Cells 12 Pages: 535-546
  • Peer Reviewed
• [Journal Article] Non-cell-autonomous action of STAT3 in maintenance of neural precursor cells in the mouse neocortex. (2006)
  • Author(s): Yoshimatsu, T., Kawaguchi, D., Oishi, K., Takeda, K., Akira, S., Masuyama, N., Gotoh, Y.
  • Journal Title: Development 133 Pages: 2553-2563
  • Peer Reviewed
• [Journal Article] JNK antagonizes Akt-mediated survival signals by phosphorylating 14-3-3. (2005)
  • Author(s): Sunayama, J., Tsuruta, F., Masuyama, N., Gotoh, Y.
  • Journal Title: J. Cell. Biol. 170 Pages: 295-304
  • Peer Reviewed
• [Presentation] Regulation and functions of the Akt/PKB pathway (2010)
  • Author(s): ukiko Gotoh
  • Organizer: AACR/JCA Joint Conference
  • Place of Presentation: Hilton Waikoloa Village, Waikoloa, Hawaii
  • Year and Date: 20100205-20100209
• [Presentation] Temporal regulation of neural stem cell fate in the mouse developing neocortex (2009)
  • Author(s): Yukiko Gotoh
  • Organizer: The International Society for Stem Cell Research 8th Annual Meeting
  • Place of Presentation: Prenary lecture, Centre Convencions Internacional Barcelona, Spain
  • Year and Date: 20090808-20090811
• [Presentation] Polycomb regulation of neural stem cell fate (2009)
  • Author(s): Yukiko Gotoh
  • Organizer: Keystone Symposia, Chromatin Dynamics and Higher Order Organization
  • Place of Presentation: Coeur d'Alene Resort, Coeur d'Alene, Idaho, USA
  • Year and Date: 20090225-20090302
• [Presentation] Temporal regulation of neocortical neural precursor cell fate (2008)
  • Author(s): Yukiko Gotoh
  • Organizer: Gordon Research Conference "Molecular and Cellular Neurobiology"
  • Place of Presentation: The Hong Kong University of Science & Technology, Hong Kong
  • Year and Date: 20080608-20080613
• [Presentation] Regulation and function of Akt (2007)
  • Author(s): Yukiko Gotoh
  • Organizer: The Federation of American Societies for Experimental Biology (FASEB), SUMMER RESEARCH CONFERENCES.
  • Place of Presentation: Hyatt Grand Champions Resort & Spa, Indian Wells Lane, Indian Wells, CA.
  • Year and Date: 20070707-20070712
• [Remarks]
  • URL: http://www.iam.u-tokyo.ac.jp/celltech/