Cell Biology

mTOR Substrates Revealed

Science Signaling  14 Jun 2011:
Vol. 4, Issue 177, pp. ec165
DOI: 10.1126/scisignal.4177ec165

The protein kinase mammalian target of rapamycin (mTOR) functions in protein complexes (mTORC1 and mTORC2) that are activated in response to agents such as growth factors and insulin and has important roles in regulating many physiological responses, including cell growth, proliferation, metabolism, and cell survival (see the Perspective by Yea and Fruman). Hsu et al. and Yu et al. conducted proteomic screens to identify substrates of mTORC1 and mTORC2 kinases. Numerous proteins that appear to be direct substrates were identified, including a new mTOR substrate, Grb10. Grb10 is an adaptor molecule that functions in the formation of signaling complexes associated with growth factor receptor tyrosine kinases.

P. P. Hsu, S. A. Kang, J. Rameseder, Y. Zhang, K. A. Ottina, D. Lim, T. R. Peterson, Y. Choi, N. S. Gray, M. B. Yaffe, J. A. Marto, D. M. Sabatini, The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317–1322 (2011). [Abstract] [Full Text]

Y. Yu, S.-O. Yoon, G. Poulogiannis, Q. Yang, X. M. Ma, J. Villén, N. Kubica, G. R. Hoffman, L. C. Cantley, S. P. Gygi, J. Blenis, Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 1322–1326 (2011). [Abstract] [Full Text]

S. S. Yea, D. A. Fruman, New mTOR targets Grb attention. Science 332, 1270–1271 (2011). [Abstract] [Full Text]