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ID 54010
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Author
Fukunaka, Ayako
Hagihara, Mitsue
Watanabe, Keiko
Kamino, Shinichiro
Kambe, Taiho
Enomoto, Shuichi Kaken ID
Hiromura, Makoto
Abstract
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.
Note
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.
Published Date
2013-03-07
Publication Title
PLOS ONE
Volume
volume8
Issue
issue3
Publisher
PUBLIC LIBRARY SCIENCE
Start Page
e58022
ISSN
1932-6203
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1371/journal.pone.0058022
language
英語
Copyright Holders
© 2013 Taniguchi et al.
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Refereed
True
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PubMed ID
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