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Elevated inorganic phosphate stimulates Akt-ERK1/2-Mnk1 signaling in human lung cells

  1. Author:
    Chang, S. H.
    Yu, K. N.
    Lee, Y. S.
    An, G. H.
    Beck, G. R.
    Colburn, N. H.
    Lee, K. H.
    Cho, M. H.

  2. Author Address

    Seoul Natl Univ, Coll Vet Med, Toxicol Lab, Seoul 151742, South Korea. Seoul Natl Univ, Coll Human Ecol, Dept Food & Nutr, Seoul 151742, South Korea. Seoul Natl Univ, BK Program Vet Sci 21, Seoul 151742, South Korea. Korea Inst Radiol & Med Sci, Mol Oncol Lab, Seoul, South Korea. Chungnam Natl Univ, Dept Food Sci & Technol, Taejon 305764, South Korea. Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA 30322 USA. NCI, Lab Canc Prevent, Frederick, MD 21701 USA.;Cho, MH, Seoul Natl Univ, Coll Vet Med, Toxicol Lab, 56-1,Sillim Dong, Seoul 151742, South Korea.;mchotox@snu.ac.kr
    1. Year: 2006
    2. Date: Nov
  2. Journal: American Journal of Respiratory Cell and Molecular Biology
    1. 35
    2. 5
    3. Pages: 528-539
  4. Type of Article: Article
  5. ISSN: 1044-1549
  1. 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 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.

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External Sources

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  2. DOI: 10.1165/rcmb.2005-04770C
  3. View record in Web of Science®
  4. WOS: 000241813300003

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