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Author Notes:

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

Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved March 21, 2008

Present address: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Chongqing 400042, China.

Author contributions: Z.M. designed research; R.L. and B.T. performed research; R.L., M.G., S.H., and K.Y. contributed new reagents/analytic tools; R.L. and Z.M. analyzed data; and R.L. and Z.M. wrote the paper.

We thank Deborah Cooper at the Center for Neurodegenerative Disease at Emory University for her help with the immunohistochemical studies and Brian Ciliax for critique of the manuscript.

The authors declare no conflict of interest.


Research Funding:

This work was supported by National Institutes of Health Grants R01 NS048254 and AG023695, and by The Robert W. Woodruff Health Sciences Center Fund (Z.M.).

Cdk5-mediated regulation of the PIKE-A-Akt pathway and glioblastoma cell invasion


Journal Title:

Proceedings of the National Academy of Sciences


Volume 105, Number 21


, Pages 7570-7575

Type of Work:

Article | Post-print: After Peer Review


Isoform A of phosphatidylinositol 3-kinase enhancer (PIKE-A) is a newly identified prooncogenic factor that has been implicated in cancer cell growth. How PIKE-A activity is regulated in response to growth signal is poorly understood. Here, we demonstrate that cyclin dependent kinase 5 (Cdk5), a protein known to function mainly in postmitotic neurons, directly phosphorylates PIKE-A at Ser-279 in its GTPase domain in glioblastoma cells. This phosphorylation event stimulates PIKE-A GTPase activity and the activity of its downstream effector Akt. Growth signal activates Cdk5 and results in a Cdk5-dependent accumulation of phosphorylated PIKE-A and activation of Akt in the nucleus. Furthermore, PIKE-A phosphorylation and Cdk5 are increased in human glioblastoma specimens. Phosphorylation of PIKE-A by Cdk5 mediates growth factor-induced migration and invasion of human glioblastoma cells. Together, these findings identify PIKE as the first Cdk5 target in cancer cells, revealing a previously undescribed regulatory mechanism that mediates growth signal-induced activation of PIKE-A/Akt and tumor invasion.

Copyright information:

© 2008 by The National Academy of Sciences of the USA

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