Functional Regulation of Erb B family by N-glycosylation
| Project/Area Number |
18590272
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
TAKAHASHI Motoko Sapporo Medical University, Department of Biochemistry, Associate Professor (00303941)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | N-glycan / glycosylation / ErbB / EGFR / dimerization / adenylyl cyclase / 糖鎖 / 増殖因子受容体 / ErbB2 / ErbB3 / 二量体形成 |
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| Research Abstract |
Glycosylation is one of the most common post-translational modification, and is known to change physico-chemical properties of proteins. In this study, I examine the function of N-glycan of ErbB family and adenylyl cyclase.
ErbB3 has 10 potential glycosylation sites in its extracellular domain. A series of human ErbB3 molecules devoid of N-glycan were prepared and transfected to Flp-In-CHO cells for stable expression. It was revealed that the Asn 418 to Gln mutant (N418Q) mutant of ErbB3 underwent ligand-independent homodimerization. When overexpressed with ErbB2, ligand-independent hetero-dimerization was observed and Erk and Akt phosphorylation was upregulated in the absence of of ErbB3 coexpressed with ErbB2 promoted cell proliferation and colony formation in soft agar in an Erk and Akt-dependent manner. The N418Q mutation also promoted the growth of tumors in athymic mice when injected subcutaneously. Thus, Asn 418-linked N-glycan in ErbB3 plays an essential role in regulating receptor heterodimerization with ErbB2 and might have an effect on transforming activity.
Adenylyl cyclase III (ACIII) has 2 potential glycosylation sites in its extracellular domain, and it was suggested that glycosylation is involved in its enzymatic activity. When processing of glycosylation was suppressed by introducing GnT-III, one of glycosyltransferases, forskolin-induced ACIII activation and downstream signaling such as the synthesis of cAMP and the phosphorylation of CREB were significantly upregulated. Now the mechanisms of the regulation of ACIII by the structure of N-glycan is being investigated.
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Report
(3 results)
Research Products
(49 results)
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[Journal Article] Functional roles of N-glycnas in cell signaling and cell adhesion in cancer2008
Author(s)
Zhao, Y., Takahashi, M., Gu, J., Miyoshi, E., Matsumoto, A., Kitazume, S., Taniguchi, N
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Journal Title
Cancer Sci. (review) (in press)
Description
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[Journal Article] The Asn418-linked N-glycan of ErbB3 plays a crucial role in preventing spontaneous heterodimerization and tumor promotion2007
Author(s)
Yokoe, S., Takahashi, M., Asahi, M., Lee, SH., Li, W., Osumi, D., Miyoshi, E., Taniguchi, N
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Journal Title
Cancer Res 20
Pages: 1935-1942
Description
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[Journal Article] Introduction of bisecting GlcNAc in N-glycans of adenylyl cyclase III enhances its activity2007
Author(s)
Li, W., Takahashi, M., Shibukawa, Y., Yokoe, S., Gu, J., Miyoshi, E., Honke, K., Ikeda, Y., Taniguchi N
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Journal Title
Glycobiology 17
Pages: 655-662
Description
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[Journal Article] Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells ; roles of p38 MAP kinase2007
Author(s)
Park, YS., Kim, J., misonou, Y., Takamiya, R., Takahashi, M., Freeman, MR., Taniguchi, N
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Journal Title
Arteriosclerosis, Thrombosis, and Vascular Biology 27
Pages: 1319-1324
Description
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[Journal Article] Gliclazide inhibits proliferation but stimulates differentiation of white and brown adipocytes2007
Author(s)
Nakano, N, Miyazawa, N., Sakurai, T., Kizaki, T., Kimoto, K., Takahashi, K., Ishida, H., Takahashi, M., Suzuki, K., Ohno, H
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Journal Title
J. Biochem 142
Pages: 639-645
NAID
Description
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[Journal Article] N-glycan of ErbB family plays a crucial role in dimer formation and tumor promotion2007
Author(s)
Takahashi, M., Yokoe, S., Asahi, M., Lee, SH., Li, W., Osumi, D., Miyoshi, E., Taniguchi, N
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Journal Title
Biochim. Biophys Acta -General Subjects (review) 1780
Pages: 520-524
Description
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[Journal Article]2007
Author(s)
Park YS., et al.
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Journal Title
Arteriolosclerosis, Thrombosis, and Vascular Biology (In Press)
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[Journal Article] Glycation and Disease
Author(s)
Takahashi, M., Suzuki, K., Ikeda, Y., Taniguchi, N.
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Journal Title
Comprehensive Glycosciences-From Chemistry to Systems Biology-2007 Elesevier Science Ltd. (Kamerling JP., Boons GJ., Lee UC., Suzuki A., Taniguchi N., Voragen AGJ. Eds.)
Description
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[Journal Article] Glycosyltransferases
Author(s)
Ikeda, Y., Takahashi, M., Taniguchi, N
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Journal Title
Comprehensive Glycosciences -From Chemistry to Systems Biology-2007 Elesevier Science Ltd., (Kamerling JP., Boons GJ., Lee UC., Suzuki A., Taniguchi N.)
Description
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[Presentation] N型糖鎖によるシグナル制御機構2007
Author(s)
高橋 素子, その他
Organizer
日本生化学会北海道支部例会
Place of Presentation
札幌市
Year and Date
2007-07-06
Description
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[Presentation] Introduction of bisecting GlcNAc in N-glycans of adenylyl cyclase III enhances its activity2007
Author(s)
Takahashi, M., Li, W., Shibukawa, Y., Yokoe, S., Gu, J., Taniguchi, N
Organizer
American Society of Biochemistry and Molecular Biology 2007(Kamerling JP., Boons GJ., Lee UC., Suzuki A., Taniguchi N., Voragen AGJ. Eds.)
Place of Presentation
Washington DC
Description
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