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The mammalian target of rapamycin (mTOR) governs cell growth and
proliferation by mediating the mitogen- and nutrient-dependentsignal
transduction that regulates messenger RNA translation.We identified
phosphatidic acid (PA) as a critical component ofmTOR signaling. In
our study, mitogenic stimulation of mammaliancells led to a
phospholipase D-dependent accumulation of cellularPA, which
was required for activation of mTOR downstream effectors.PA directly
interacted with the domain in mTOR that is targetedby rapamycin, and
this interaction was positively correlated withmTOR's ability to
activate downstream effectors. The involvementof PA in mTOR signaling
reveals an important function of thislipid in signal transduction and
protein synthesis, as well asa direct link between mTOR and mitogens.
Furthermore, these studiessuggest a potential mechanism for the in
vivo actions of the immunosuppressantrapamycin.
Department of Cell and Structural Biology, University of Illinois
at Urbana-Champaign, 601 South Goodwin Avenue, B107, Urbana, IL 61801, USA.
*
To whom correspondence should be addressed. E-mail:
jiechen{at}uiuc.edu
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