2009 Fiscal Year Final Research Report
The Molecular basis of tyrosine kinase signaling
| Project/Area Number |
17012015
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
OKADA Masato Osaka University, 微生物病研究所, 教授 (10177058)
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| Project Period (FY) |
2005 – 2009
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| Keywords | チロシンキナーゼ / がん遺伝子 / ラフト / シグナル伝達 / Src / Cbp / Csk / エンドソーム |
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| Research Abstract |
To elucidate the molecular basis for the regulatory mechanisms of Src-mediated tumor progression, we analyzed the function of a transmembrane raft adaptor Cbp (Csk binding protein), and a novel membrane adaptor p18 which was identified from lipid rafts of late endosomes. We found that Cbp expression is downregulated via some oncogenic pathways, and that Cbp suppresses Src function by sequestering activated Src to lipid rafts. These findings suggest that Cbp functions as a type of tumor suppressor. We also found that p18 plays a crucial role in regulating endosome dynamics as well as cell growth by recruiting Src/Ras-MEK1-ERK pathway to late endosomes. These results indicate that the p18 pathway is crucial for regulating cell transformation and tumor growth.
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[Journal Article] A versatile nonviral vector system for tetracycline-dependent one-step conditional induction of transgene expression.2009
Author(s)
Inoue K, Sone T, Oneyama C, Nishiumi F, Kishine H, Sasaki Y,, oh T, Okada M, Chesnut JD, Imamoto F.
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Journal Title
Gene Therapy 16
Pages: 1383-1394
Peer Reviewed
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[Journal Article] Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling.2009
Author(s)
Enomoto M, Hayakawa S, Itsukushima S, Ren DY, Matsuo M, Tamada K, Oneyama C, Okada M, Takumi T, Nishita M, Minami Y.
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Journal Title
Oncogene 28
Pages: 3197-3208
Peer Reviewed
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[Journal Article] Structural insight into the specific interaction between murine SHPS-1/SIRPa and its ligand CD47.2008
Author(s)
Nakaishi A, Hirose M, Yoshimura M, Oneyama C, Saito K, Kuki N, Matsuda M, Honma N, Ohnishi H, Matozaki T, Okada M, Nakagawa A.
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Journal Title
J. Mol. Biol. 375
Pages: 650-660
Peer Reviewed
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[Journal Article] Targeting AMAP1 and cortactin binding bearing an atypical src homology 3/proline interface for prevention of breast cancer invasion and metastasis.2006
Author(s)
Hashimoto S, Hirose M, Hashimoto A, Morishige M, Yamada A, Hosaka H, Akagi K, Ogawa E, Oneyama C, Agatsuma T, Okada M, Kobayashi H, Wada H, Nakano H, Ikegami T, Nakagawa A, Sabe H.
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Journal Title
Proc Natl Acad Sci U S A. 103
Pages: 7036-7041
Peer Reviewed
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[Journal Article] Cardiac Ischemia Activates Vascular Endothelial Cadherin Promoter in Both Preexisting Vascular Cells and Bone Marrow Cells Involved in Neovascularization.2006
Author(s)
Kogata N, Arai Y, Pearson J.T., Hashimoto K, Hidaka K, Koyama T, Somekawa S, Nakaoka Y, Ogawa M, Adams R.H., Okada M, Mochizuki N.
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Journal Title
Circ Res. 98
Pages: 897-904
Peer Reviewed
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