S-Space College of Veterinary Medicine (수의과대학) Dept. of Veterinary Medicine (수의학과) Journal Papers (저널논문_수의학과)
Elevated inorganic phosphate stimulates Akt-ERK1/2-Mnk1 signaling in human lung cells
- Chang, Seung-Hee; Yu, Kyeong Nam; Lee, Yeon-Sook; An, Gil-Hwan; Beck, George R., Jr.; Colburn, Nancy H.; Lee, Kee-Ho; Cho, Myung-Haing
- Issue Date
- American Thoracic Society
- American Journal of Respiratory Cell and Molecular Biology, Vol.35 No.5, pp.528-539
- 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 elF4E-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.
- Files in This Item: There are no files associated with this item.