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Molecular and Cellular Biology, April 2005, p. 3151-3162, Vol. 25, No. 8
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.8.3151-3162.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Akt-Dependent Cell Size Regulation by the Adhesion Molecule on Glia Occurs Independently of Phosphatidylinositol 3-Kinase and Rheb Signaling

Danielle K. Scheidenhelm,1 Jennifer Cresswell,1 Carrie A. Haipek,1 Timothy P. Fleming,2 Robert W. Mercer,3 and David H. Gutmann1*

Departments of Neurology,1 Surgery,2 Cell Biology, Washington University School of Medicine, St. Louis, Missouri3

Received 30 August 2004/ Returned for modification 12 October 2004/ Accepted 6 January 2005

The role of cell adhesion molecules in mediating interactions with neighboring cells and the extracellular matrix has long been appreciated. More recently, these molecules have been shown to modulate intracellular signal transduction cascades critical for cell growth and proliferation. Expression of adhesion molecule on glia (AMOG) is downregulated in human and mouse gliomas, suggesting that AMOG may be important for growth regulation in the brain. In this report, we examined the role of AMOG expression on cell growth and intracellular signal transduction. We show that AMOG does not negatively regulate cell growth in vitro or in vivo. Instead, expression of AMOG in AMOG-deficient cells results in a dramatic increase in cell size associated with protein kinase B/Akt hyperactivation, which occurs independent of phosphatidylinositol 3-kinase activation. AMOG-mediated Akt phosphorylation specifically activates the mTOR/p70S6 kinase pathway previously implicated in cell size regulation, but it does not depend on tuberous sclerosis complex/Ras homolog enriched in brain (Rheb) signaling. These data support a novel role for a glial adhesion molecule in cell size regulation through selective activation of the Akt/mTOR/S6K signal transduction pathway.

* Corresponding author. Mailing address: Department of Neurology, Washington University School of Medicine, Box 8111, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-7379. Fax: (314) 362-2388. E-mail: gutmannd{at}neuro.wustl.edu.

Molecular and Cellular Biology, April 2005, p. 3151-3162, Vol. 25, No. 8
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.8.3151-3162.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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