Editors' ChoicePharmacology

Not mTORCing

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Science Signaling  30 Jul 2013:
Vol. 6, Issue 286, pp. ec178
DOI: 10.1126/scisignal.2004548

Inhibition of the protein kinase complex mTORC1 has potentially beneficial therapeutic effects that include inhibition of cancer and extension of life span. However, effects of its inhibition in vivo have sometimes been disappointing. One reason may be that the well-studied inhibitor of mTORC1, rapamycin, inhibits some effects of mTORC1 but not others. In line with this idea, Kang et al. show that the effect of rapamycin depends on the substrate. Characteristics of the phosphorylation sites on various substrates caused them to be phosphorylated with different efficiency by mTORC1. The substrates that were most efficiently phosphorylated were resistant to inhibition of mTORC1. The results explain how various sites, sometimes within the same protein, can differ in their sensitivity to rapamycin.

S. A. Kang, M. E. Pacold, C. L. Cervantes, D. Lim, H. J. Lou, K. Ottina, N. S. Gray, B. E. Turk, M. B. Yaffe, D. M. Sabatini, mTORC1 phosphorylation sites encode their sensitivity to starvation and rapamycin. Science 341, 1236566 (2013). [Abstract] [Full Text]

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