DOI: 10.1073/pnas.0802533105. Akt phosphorylation and nuclear phosphoinositide association mediate mRNA export and cell proliferation activities by ALY

Akt phosphorylation and nuclear phosphoinositide association mediate mRNA export and cell proliferation activities by ALY

10.1073/pnas.0802533105

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Nuclear PI3K and its downstream effectors play essential roles in a variety of cellular activities including cell proliferation, survival, differentiation, and pre-mRNA splicing. Aly is a nuclear speckle protein implicated in mRNA export. Here we show that Aly is a physiological target of nuclear PI3K signaling, which regulates its subnuclear residency, cell proliferation, and mRNA export activities through nuclear Akt phosphorylation and phosphoinositide association. Nuclear Akt phosphorylates Aly on threonine-219, which is required for its interaction with Akt. Aly binds phosphoinositides, and this action is regulated by Akt-mediated phosphorylation. Phosphoinositide binding but not Akt phosphorylation dictates Aly's nuclear speckle residency. Depletion of Aly results in cell growth suppression and mRNA export reduction. Inhibition of Aly phosphorylation substantially decreases cell proliferation and mRNA export. Furthermore, disruption of phosphoinositide association with Aly also significantly reduces these activities. Thus, nuclear PI3K signaling mediates both cell proliferation and mRNA export functions of Aly.

Bibliography

Okada, M., Jang, S.-W., & Ye, K. (2008). Akt phosphorylation and nuclear phosphoinositide association mediate mRNA export and cell proliferation activities by ALY. Proceedings of the National Academy of Sciences, 105(25), 8649â8654.

Authors 3

Masashi Okada (first)
Sang-Wuk Jang (additional)
Keqiang Ye (additional)

References 33 Referenced 97

Dates

Type	When
Created	17 years, 2 months ago (June 17, 2008, 8:45 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 4:43 p.m.)
Indexed	3 weeks, 5 days ago (July 27, 2025, 3:51 a.m.)
Issued	17 years, 1 month ago (June 24, 2008)
Published	17 years, 1 month ago (June 24, 2008)
Published Online	17 years, 1 month ago (June 24, 2008)
Published Print	17 years, 1 month ago (June 24, 2008)

Funders 0

None

BibTeX

@article{Okada_2008, title={Akt phosphorylation and nuclear phosphoinositide association mediate mRNA export and cell proliferation activities by ALY}, volume={105}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0802533105}, DOI={10.1073/pnas.0802533105}, number={25}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Okada, Masashi and Jang, Sang-Wuk and Ye, Keqiang}, year={2008}, month=jun, pages={8649–8654} }

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