Abstract
The mammalian target of rapamycin complex 1 (mTORC1) senses nutrients to mediate anabolic processes within the cell. Exactly how mTORC1 promotes cell growth remains unclear. Here, we identified a novel mTORC1-interacting protein called A-kinase anchoring protein 8L (AKAP8L). Using biochemical assays, we found that the N-terminal region of AKAP8L binds to mTORC1 in the cytoplasm. Importantly, loss of AKAP8L decreased mTORC1-mediated processes such as translation, cell growth and cell proliferation. AKAPs anchor protein kinase A (PKA) through PKA regulatory subunits, and we show that AKAP8L can anchor PKA through regulatory subunit Ia. Reintroducing full-length AKAP8L into cells restored mTORC1-regulated activities, whereas reintroduction of AKAP8L missing the N-terminal region that confers the interaction with mTORC1 did not. Our results suggest a multifaceted role for AKAPs in the cell. We conclude that mTORC1 appears to regulate protein translation, perhaps in part through AKAP8L.
Original language | English (US) |
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Pages (from-to) | 8096-8105 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 295 |
Issue number | 23 |
DOIs | |
State | Published - Apr 2020 |
Keywords
- A-kinase anchoring protein (AKAP)
- AKAP8L
- Anabolic pathway
- CAMP signaling
- Cell proliferation
- Cell size
- MRNA translation
- MTORC1
- Nutrient sensing
- Scaffolding protein
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology