Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin

Gregory J. Brunn, Christine C. Hudson, Aleksandar Sekulić, Josie M. Williams, Hajime Hosoi, Peter J. Houghton, John C. Lawrence, Robert T. Abraham

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Abstract

The immunosuppressant rapamycin interferes with G1-phase progression in lymphoid and other cell types by inhibiting the function of the mammalian target of rapamycin (mTOR). mTOR was determined to be a terminal kinase in a signaling pathway that couples mitogenic stimulation to the phosphorylation of the eukaryotic initiation factor (eIF)-4E-binding protein, PHAS-I. The rapamycin-sensitive protein kinase activity of roTOR was required for phosphorylation of PHAS-I in insulin-stimulated human embryonic kidney cells. mTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E. These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells.

Original languageEnglish (US)
Pages (from-to)99-101
Number of pages3
JournalScience
Volume277
Issue number5322
DOIs
StatePublished - Jul 4 1997

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Cite this

Brunn, G. J., Hudson, C. C., Sekulić, A., Williams, J. M., Hosoi, H., Houghton, P. J., Lawrence, J. C., & Abraham, R. T. (1997). Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science, 277(5322), 99-101. https://doi.org/10.1126/science.277.5322.99