Published ahead of print on June 8, 2006, doi:10.1165/rcmb.2005-0477OC Am. J. Respir. Cell Mol. Biol., Volume 35, Number 5, November 2006, 528-539 A more recent version of this article appeared on November 1, 2006
Submitted on December 21, 2005 Elevated Inorganic Phosphate Stimulates AKT-ERK1/2-Mnk1 Signaling in Human Lung CellsSeung-Hee Chang1,1 Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea, Republic of, 2 Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea, Republic of, 3 Department of Food Science and Technology, Chungnam National University, Taejeon, Korea, Republic of, 4 Division of Endocrinology, Metabolism, and Lipids, Emory University School of Medicine, Atlanta, GA, USA, 5 Laboratory of Cancer Prevention, National Cancer Institute, Frederick, MD, USA, 6 Laboratory of Molecular Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea, Republic of * To whom correspondence should be addressed. E-mail: mchotox{at}snu.ac.kr.
Inorganic phosphate (Pi) plays a critical role in diverse cellular functions. Among 3 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 normal 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 capdependent protein translation. Such Akt-mediated signaling of inorganic phosphate may provide critical clues for treatment as well as prevention of diverse lung diseases.
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
