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mTOR kinase-dependent, but raptor-independent regulation of downstream signaling is important for cell cycle exit and myogenic differentiation

mTOR kinase-dependent, but raptor-independent regulation of downstream signaling is important for cell cycle exit and myogenic differentiation
mTOR kinase-dependent, but raptor-independent regulation of downstream signaling is important for cell cycle exit and myogenic differentiation
Myogenic differentiation in the C2C12 myoblast model system reflects a concerted and controlled activation of transcription and translation following the exit of cells from the cell cycle. Previously we have shown that the mTORC1 signaling inhibitor, RAD001, decreased protein synthesis rates, delayed C2C12 myoblast differentiation, decreased p70S6K activity but did not affect the hypermodification of 4E-BP1. Here we have further investigated the modification of 4E-BP1 during the early phase of differentiation as cells exit the cell cycle, using inhibitors to target mTOR kinase and siRNAs to ablate the expression of raptor and rictor. As predicted, inhibition of mTOR kinase activity prevented p70S6K, 4E-BP1 phosphorylation and was associated with an inhibition of myogenic differentiation. Surprisingly, extensive depletion of raptor did not affect p70S6K or 4E-BP1 phosphorylation, but promoted an increase in mTORC2 activity (as evidenced by increased Akt Ser473 phosphorylation). These data suggest that an mTOR kinase-dependent, but raptor-independent regulation of downstream signaling is important for myogenic differentiation.
1538-4101
2517-2525
Pollard, H.J.
014c948c-52ac-4367-8610-9a20f7315dee
Willett, M.
dfa36c04-719a-4884-87cd-2ae13a3d2b67
Morley, S.J.
4619ce88-4e00-4e13-b8b3-71b768afd705
Pollard, H.J.
014c948c-52ac-4367-8610-9a20f7315dee
Willett, M.
dfa36c04-719a-4884-87cd-2ae13a3d2b67
Morley, S.J.
4619ce88-4e00-4e13-b8b3-71b768afd705

Pollard, H.J., Willett, M. and Morley, S.J. (2014) mTOR kinase-dependent, but raptor-independent regulation of downstream signaling is important for cell cycle exit and myogenic differentiation. Cell Cycle, 13 (16), 2517-2525. (doi:10.4161/15384101.2014.941747).

Record type: Article

Abstract

Myogenic differentiation in the C2C12 myoblast model system reflects a concerted and controlled activation of transcription and translation following the exit of cells from the cell cycle. Previously we have shown that the mTORC1 signaling inhibitor, RAD001, decreased protein synthesis rates, delayed C2C12 myoblast differentiation, decreased p70S6K activity but did not affect the hypermodification of 4E-BP1. Here we have further investigated the modification of 4E-BP1 during the early phase of differentiation as cells exit the cell cycle, using inhibitors to target mTOR kinase and siRNAs to ablate the expression of raptor and rictor. As predicted, inhibition of mTOR kinase activity prevented p70S6K, 4E-BP1 phosphorylation and was associated with an inhibition of myogenic differentiation. Surprisingly, extensive depletion of raptor did not affect p70S6K or 4E-BP1 phosphorylation, but promoted an increase in mTORC2 activity (as evidenced by increased Akt Ser473 phosphorylation). These data suggest that an mTOR kinase-dependent, but raptor-independent regulation of downstream signaling is important for myogenic differentiation.

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Published date: 30 October 2014
Organisations: Centre for Biological Sciences

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Local EPrints ID: 371738
URI: http://eprints.soton.ac.uk/id/eprint/371738
ISSN: 1538-4101
PURE UUID: a542b005-6a89-4264-a1c2-3bf7c6f4aeb1

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Date deposited: 13 Nov 2014 12:16
Last modified: 15 Jul 2019 21:38

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