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ID 54010
フルテキストURL
著者
Taniguchi, Masanari Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University ORCID 科研費研究者番号 publons
Fukunaka, Ayako Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science
Hagihara, Mitsue Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science
Watanabe, Keiko Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science
Kamino, Shinichiro Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science
Kambe, Taiho Graduate School of Biostudies, Kyoto University
Enomoto, Shuichi Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University 科研費研究者番号
Hiromura, Makoto Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science
抄録
The essential trace element zinc is important for all living organisms. Zinc functions not only as a nutritional factor, but also as a second messenger. However, the effects of intracellular zinc on the B cell-receptor (BCR) signaling pathway remain poorly understood. Here, we present data indicating that the increase in intracellular zinc level induced by ZIP9/SLC39A9 (a ZIP Zrt-/Irt-like protein) plays an important role in the activation of Akt and Erk in response to BCR activation. In DT40 cells, the enhancement of Akt and Erk phosphorylation following BCR activation requires intracellular zinc. To clarify this event, we used chicken ZnT5/6/7-gene-triple-knockout DT40 (TKO) cells and chicken Zip9-knockout DT40 (cZip9KO) cells. The levels of Akt and ERK phosphorylation significantly decreased in cZip9KO cells. In addition, the enzymatic activity of protein tyrosine phosphatase (PTPase) increased in cZip9KO cells. These biochemical events were restored by overexpressing the human Zip9 (hZip9) gene. Moreover, we found that the increase in intracellular zinc level depends on the expression of ZIP9. This observation is in agreement with the increased levels of Akt and Erk phosphorylation and the inhibition of total PTPase activity. We concluded that ZIP9 regulates cytosolic zinc level, resulting in the enhancement of Akt and Erk phosphorylation. Our observations provide new mechanistic insights into the BCR signaling pathway underlying the regulation of intracellular zinc level by ZIP9 in response to the BCR activation.
備考
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
発行日
2013-03-07
出版物タイトル
PLOS ONE
8巻
3号
出版者
PUBLIC LIBRARY SCIENCE
開始ページ
e58022
ISSN
1932-6203
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1371/journal.pone.0058022
言語
English
著作権者
© 2013 Taniguchi et al.
論文のバージョン
publisher
査読
有り
DOI
PubMed ID
Web of Sience KeyUT