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Updated: Aug 11, 2025

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases
Published on: September 6, 2024
Regulation of mTOR by phosphatidic acid
Maria A Frias1, Ahmet Hatipoglu2, David A Foster3
1Department of Biology and Health Promotion, St. Francis College, Brooklyn, NY 11201, USA; Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10065, USA.
Abstract:
mTORC1, the mammalian target of rapamycin complex 1, is a key regulator of cellular physiology. The lipid metabolite phosphatidic acid (PA) binds to and activates mTORC1 in response to nutrients and growth factors. We review structural findings and propose a model for PA activation of mTORC1. PA binds to a highly conserved sequence in the α4 helix of the FK506 binding protein 12 (FKBP12)/rapamycin-binding (FRB) domain of mTOR. It is proposed that PA binding to two adjacent positively charged amino acids breaks and shortens the C-terminal region of helix α4. This has profound consequences for both substrate binding and the catalytic activity of mTORC1.
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