» Articles » PMID: 32312749

A-kinase Anchoring Protein 8L Interacts with MTORC1 and Promotes Cell Growth

Overview
Journal J Biol Chem
Specialty Biochemistry
Date 2020 Apr 22
PMID 32312749
Citations 15
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Human cells contain myriad excised linear intron RNAs with links to gene regulation and potential utility as biomarkers.

Yao J, Xu H, Ferrick-Kiddie E, Nottingham R, Wu D, Ares Jr M PLoS Genet. 2024; 20(9):e1011416.

PMID: 39325823 PMC: 11460701. DOI: 10.1371/journal.pgen.1011416.


Microglial AKAP8L: a key mediator in diabetes-associated cognitive impairment via autophagy inhibition and neuroinflammation triggering.

Zhang W, Wei Q, Zhang T, Wang C, Chen J, Wang J J Neuroinflammation. 2024; 21(1):177.

PMID: 39033121 PMC: 11264944. DOI: 10.1186/s12974-024-03170-z.


InDel and CNV within the Gene Revealing Strong Associations with Growth Traits in Goat.

Song X, Bai Y, Yuan R, Zhu H, Lan X, Qu L Animals (Basel). 2023; 13(17).

PMID: 37685010 PMC: 10487263. DOI: 10.3390/ani13172746.


Integrative analysis identifies AKAP8L as an immunological and prognostic biomarker of pan-cancer.

Zhou L, Mei J, Cao R, Liu X, Fu B, Ma M Aging (Albany NY). 2023; 15(17):8851-8872.

PMID: 37683130 PMC: 10522372. DOI: 10.18632/aging.205003.


Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders.

Pintacuda G, Hsu Y, Tsafou K, Li K, Martin J, Riseman J Cell Genom. 2023; 3(3):100250.

PMID: 36950384 PMC: 10025425. DOI: 10.1016/j.xgen.2022.100250.


References
1.
Yu F, Zhang Y, Park H, Jewell J, Chen Q, Deng Y . Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. Genes Dev. 2013; 27(11):1223-32. PMC: 3690396. DOI: 10.1101/gad.219402.113. View

2.
Hsu P, Kang S, Rameseder J, Zhang Y, Ottina K, Lim D . The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science. 2011; 332(6035):1317-22. PMC: 3177140. DOI: 10.1126/science.1199498. View

3.
Malbon C, Tao J, Wang H . AKAPs (A-kinase anchoring proteins) and molecules that compose their G-protein-coupled receptor signalling complexes. Biochem J. 2004; 379(Pt 1):1-9. PMC: 1224059. DOI: 10.1042/BJ20031648. View

4.
Coghlan V, Langeberg L, Fernandez A, Lamb N, Scott J . Cloning and characterization of AKAP 95, a nuclear protein that associates with the regulatory subunit of type II cAMP-dependent protein kinase. J Biol Chem. 1994; 269(10):7658-65. View

5.
Thoreen C, Chantranupong L, Keys H, Wang T, Gray N, Sabatini D . A unifying model for mTORC1-mediated regulation of mRNA translation. Nature. 2012; 485(7396):109-13. PMC: 3347774. DOI: 10.1038/nature11083. View