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Author Notes:

To whom correspondence should be addressed. E-mail: kye@emory.edu

Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved April 23, 2008

Author contributions: M.O., S.-W.J., and K.Y. designed research; M.O. and S.-W.J. performed research; M.O., S.-W.J., and K.Y. analyzed data; and M.O. and K.Y. wrote the paper.

We are thankful to Dr. Rozanne M. Sandri-Goldin (University of California, Irvine, CA) for EGFP-ALY and Flag-ALY constructs and Dr. Michael Green from (University of Massachusetts, Worcester, MA) for the pRSETC-BEF/ALY construct.

Subjects:

Research Funding:

This work was supported by National Institutes of Health Grant RO1 NS045627 (to K.Y.).

Keywords:

  • nuclear PI 3-kinase
  • nuclear speckle
  • nuclear Akt
  • T219 phosphorylation

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

Tools:

Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 105, Number 25

Publisher:

, Pages 8649-8654

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2008 by The National Academy of Sciences of the USA

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