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Elevated Inorganic Phosphate Stimulates Akt-ERK1/2-Mnk1 Signaling in Human Lung Cells

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Authors
Chang, Seung-Hee; Yu, Kyeong Nam; Lee, Yeon-Sook; An, Gil-Hwan; Beck, George R.; Colburn, Nancy H.; Lee, Kee-Ho; Cho, Myung-Haing
Issue Date
2006
Publisher
American Thoracic Society
Citation
Am J Resp Cell Mol Biol 2006;35:528-539
Keywords
Aktinorganic phosphateMnk1nontumorigenic human bronchial epithelial cells
Abstract
Inorganic phosphate (Pi) plays a critical role in diverse cellular functions. Among three classes of sodium/phosphate co-transporters (NPTs), two types have been identified in mammalian lung. The potential importance of Pi as a novel signaling molecule and pulmonary expression of NPTs with poor prognosis of diverse lung diseases including cancer have prompted us to begin to define the pathways by which Pi regulates nontumorigenic human bronchial epithelial cells. Pi activates Akt phosphorylation on Thr308 specifically, and activated signal transmits on the Raf/MEK/ERK signaling. Here, we report that Pi controls cell growth by activating ERK cascades and by facilitating the translocation of Mnk1 from cytosol into nucleus through an Akt-mediated MEK pathway. Sequentially, translocated Mnk1 increases eIF4E-BP1 phosphorylation. As a result, Pi stimulates cap-dependent protein translation. Such Akt-mediated signaling of inorganic phosphate may provide critical clues for treatment as well as prevention of diverse lung diseases.
ISSN
1044-1549
Language
English
URI
http://hdl.handle.net/10371/6503
DOI
https://doi.org/10.1165/rcmb.2005-0477OC
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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