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J Biol Chem. 2009 Sep 4;284(36):24512-25. doi: 10.1074/jbc.M109.026237. Epub 2009 Jul 10.

Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons.

Author information

1
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Abstract

Terminally differentiated neurons are unable to reenter the cell cycle. Aberrant cell cycle activation provokes neuronal cell death, whereas cell cycle inhibition elevates neuronal survival. However, the molecular mechanism regulating the cell cycle and cell death in mature neurons remains elusive. Here we show that SRPK2, a protein kinase specific for the serine/arginine (SR) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin D1. Akt phosphorylates SRPK2 on Thr-492 and promotes its nuclear translocation leading to cyclin D1 up-regulation, cell cycle reentry, and neuronal apoptosis. In addition, SRPK2 phosphorylates SC35 and, thus, inactivates p53, resulting in cyclin D1 up-regulation. 14-3-3 binding to SRPK2, regulated by Akt phosphorylation, inhibits these events. We find that SRPK2 is phosphorylated in ischemia-attacked brain, correlating with the observed increase in cyclin D1 levels. Hence, phosphatidylinositol 3-kinase/Akt mediates the cell cycle and cell death machinery in the nervous system through phosphorylation of SRPK2.

PMID:
19592491
PMCID:
PMC2782043
DOI:
10.1074/jbc.M109.026237
[Indexed for MEDLINE]
Free PMC Article

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