Investigation of regulatory mechanisms of WNK signal by insulin
Project/Area Number |
26860628
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Kidney internal medicine
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Nishida Hidenori 東京医科歯科大学, 医歯(薬)学総合研究科, 非常勤講師 (40707379)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 塩分感受性高血圧 / WNK / KLHL3 / インスリン / 質量分析 / 塩分感受性 / WNKキナーゼ |
Outline of Final Research Achievements |
Mutations in WNK1, WNK4, KLHL3, and Cullin3 result in an inherited hypertensive disease, pseudohypoaldosteronism type II. WNK activates the Na-Cl cotransporter (NCC) in the kidney. Further, KLHL3 binds to WNKs as an adapter protein of Cullin3-based E3 ubiquitin ligase and degrades them. Insulin have been identified as powerful activator of WNK signaling. In this study, we investigated effects of Akt, key downstream substrates of insulin, on KLHL3. Mass spectrometry analysis revealed KLHL3 phosphorylation at S433. Phospho-specific antibody demonstrated defective binding between phosphorylated KLHL3 and WNK4. in vitro kinase assay demonstrated that Akt can phosphorylate KLHL3 at S433. Insulin also increased phosphorylation of KLHL3 at S433 in cultured cells. This could be a novel mechanism on how insulin physiologically activate the WNK signal.
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Report
(3 results)
Research Products
(6 results)
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[Journal Article] Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3.2015
Author(s)
Yoshizaki Y, Mori Y, Tsuzaki Y, Mori T, Nomura N, Wakabayashi M, Takahashi D, Zeniya M, Kikuchi E, Araki Y, Ando F, Isobe K, Nishida H, Ohta A, Susa K, Inoue Y, Chiga M, Rai T, Sasaki S, Uchida S, Sohara E.
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Journal Title
Biochem Biophys Res Commun.
Volume: 467
Issue: 2
Pages: 229-234
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Kelch-Like Protein 2 Mediates Angiotensin II-With No Lysine 3 Signaling in the Regulation of Vascular Tonus2015
Author(s)
Zeniya M, Morimoto N, Takahashi D, Mori Y, Mori T, Ando F, Araki Y, Yoshizaki Y, Inoue Y, Isobe K, Nomura N, Oi K, Nishida H, Sasaki S, Sohara E, Rai T, Uchida S
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Journal Title
J Am Soc Nephrol
Volume: 26
Issue: 9
Pages: 2129-2138
DOI
Related Report
Peer Reviewed
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[Journal Article] Impaired degradation of WNK1 and WNK4 kinases causes PHAII in mutant KLHL3 knock-in mice2014
Author(s)
Susa K, Sohara E, Rai T, Zeniya M, Mori Y, Mori T, Chiga M, Nomura N, Nishida H, Takahashi D, Isobe K, Inoue Y, Takeishi K, Takeda N, Sasaki S, Uchida S
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Journal Title
Hum Mol Genet
Volume: 23 (19)
Issue: 19
Pages: 5052-60
DOI
Related Report
Peer Reviewed
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[Presentation] KLHL2 mediates angiotensin II-WNK3 singaling involved in the regulation of vascular tonus2014
Author(s)
Zeniya M, Morimoto N, Takahashi D, Mori Y, Mori T, Ando F, Araki Y, Yoshizaki Y, Inoue Y, Ishobe K, Nomura N, Oi K, Nishida H, Sasaki S, Sohara E, Rai T, Uchida S.
Organizer
The 47th Annual Meeting of American Society of Nephrology
Place of Presentation
Philadelphia、米国
Year and Date
2014-11-13 – 2014-11-16
Related Report
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[Presentation] Anemia management and cardiovascular risk in newly visited CKD patients in Japan.2014
Author(s)
Iimori S, Nishida H, Yamamura C, Kihira H, Yui N, Ohta A, Okado T, Noda Y, Rai T, Uchida S, Sasaki S.
Organizer
The 14th Asian Pacific Congress of Nephrology
Place of Presentation
品川プリンスホテル、Tokyo
Year and Date
2014-05-14 – 2014-05-17
Related Report