NDLI: Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells

Content Provider	PubMed Central
Author	Wang, Lihong Fraley, Cresson D. Faridi, Jesika Kornberg, Arthur Roth, Richard A.
Copyright Year	2003
Abstract	Inorganic polyphosphate (poly P), chains of hundreds of phosphate residues linked by “high-energy” bonds as in ATP, has been conserved from prebiotic times in all cells. Poly P is essential for a wide variety of functions in bacteria, including virulence in pathogens. In this study, we observe the unique and many-fold stimulation by poly P in vitro of the protein kinase mTOR (mammalian target of rapamycin). To explore the role of poly P in mammalian cells, a yeast polyphosphatase, PPX1, was inserted into the chromosomes of MCF-7 mammary cancer cells. The transfected cells are markedly deficient in their response to mitogens, such as insulin and amino acids, as seen in their failure to activate mTOR to phosphorylate one of its substrates, PHAS-I (the initiation factor 4E-binding protein). In addition, the transfected cells are severely reduced in their growth in a serum-free medium. On the basis of these findings, we suggest that poly P (and/or PPX1) serves as a regulatory factor in the activation of mTOR in the proliferative signaling pathways of animal cells.
Related Links	http://dx.doi.org/10.1073/pnas.1534805100
Ending Page	11254
Page Count	6
Starting Page	11249
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	20
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-09-30
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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