New Insights into the GH-IGF1 axis of Signal Transduction: Elucidation of the Molecular Interactions
| Project/Area Number |
25461394
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
Jing Xuefeng 和歌山県立医科大学, 先端医学研究所, 准教授 (70316123)
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| Co-Investigator(Kenkyū-buntansha) |
澤田 貴宏 和歌山県立医科大学, 先端医学研究所, 非常勤講師 (00382325)
古島 謙亮 和歌山県立医科大学, 医学部, 助教 (50392105)
坂口 和成 和歌山県立医科大学, 先端医学研究所, 教授 (60178548)
宮嶋 正康 和歌山県立医科大学, 共同利用施設, 准教授 (80137257)
新井 大貴 和歌山県立医科大学, 先端医学研究所, 学内助教 (90725574)
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| Research Collaborator |
Frank Stuart J. University of Alabama at Birmingham, Department of Medicine, Division of Endocrinology and Metabolism, MD. Professor and Director
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | EphA4 / GHR / JAK2 / STAT5B / GH-IGF1 / GH-IGF1 軸 / ATAT5B / Eph / ephrin / 分子間相互作用 / GH-IGF1軸シグナル伝達系 |
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| Outline of Final Research Achievements |
We previously reported that EphA4, a member of the Eph family of RTK, is an important modulator of growth hormone (GH) signaling, leading to augmented synthesis of IGF1 for postnatal body growth. We report here the molecular interactions of EphA4, GH receptor (GHR), JAK2 and STAT5B. EphA4 binds to GHR at both its extracellular and intracellular domains and phosphorylates GHR when stimulated with a ligand. The cytoplasmic domain of EphA4 binds to the carboxy-terminus of JAK2. STAT5B binds to the amino-terminal kinase domain of EphA4. Ligand-activated EphA4 and JAK2 phosphorylate each other and STAT5B, but JAK2 does not appear to phosphorylate EphA4-bound STAT5B. Ligand-activated EphA4 induces the nuclear translocation of STAT5B in a JAK2-independent manner. GHR expression is required for the activation of STAT5B signaling, even via the JAK2-independent pathway. These findings suggest the molecular mechanisms by which ephrin/EphA4 signaling enhances the canonical GH-IGF1 axis.
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Report
(5 results)
Research Products
(11 results)
