A-kinase anchoring protein 8L interacts with mTORC1 and promotes cell growth

Chase H. Melick, Delong Meng, Jenna L. Jewell

Research output: Contribution to journalArticle

Abstract

mTOR 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 protein kinase A 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 Iα. Reintroducing full-length AKAP8L into cells restored mTORC1-regulated processes, 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 cell growth, perhaps in part through AKAP8L.

Original languageEnglish (US)
Pages (from-to)8096-8105
Number of pages10
JournalThe Journal of biological chemistry
Volume295
Issue number23
DOIs
StatePublished - Jun 5 2020

Keywords

  • A-kinase anchoring protein (AKAP)
  • AKAP8L
  • anabolic pathway
  • cAMP signaling
  • cell biology
  • cell proliferation
  • cell size
  • mRNA translation
  • mTOR complex (mTORC)
  • mTORC1
  • nutrient sensing
  • protein kinase A (PKA)
  • protein synthesis
  • scaffolding protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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