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Glycogen Synthase Kinase 3β (GSK3β) Regulates Differentiation and Proliferation in Neural Stem Cells from the Rat Subventricular Zone

Martin H. Maurer,*^† Jens O. Brömme,^†^§ Robert E. Feldmann, Jr.,^†^§ Anne Järve,^† Fatemeh Sabouri,^† Heinrich F. Bürgers,^† Dominik W. Schelshorn,^† Carola Krüger,^‡ Armin Schneider,^‡ and Wolfgang Kuschinsky^†

Department of Physiology and Pathophysiology, Division of Systems Physiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany, and SYGNIS Pharma AG, Im Neuenheimer Feld 515, Heidelberg, Germany

J. Proteome Res., 2007, 6 (3), pp 1198–1208

DOI: 10.1021/pr0605825

Publication Date (Web): January 18, 2007

To whom correspondence should be addressed. Dr. Martin H. Maurer, Dept. of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany. Phone: +49-6221-544075. Fax: +49-6221-544561. E-mail: maurer@physiologie.uni-heidelberg.de.

†

University of Heidelberg.

Equal cotntributions.

‡

SYGNIS Pharma AG.

Abstract

On the basis of its inhibition by SB216763, we identified the multifunctional enzyme Glycogen Synthase Kinase 3β (GSK3β) as a central regulator for differentiation and cell survival of adult neural stem cells. Detected by proteomic approaches, members of the Wnt/β-catenin signaling pathway appear to participate in enhanced neuronal differentiation and activated transcription of β-catenin target genes during GSK3β inhibition, associated with decreased apoptosis.

Keywords: Neural stem cell • Neurosphere • Glycogen Synthase Kinase 3β • Two-dimensional gel electrophoresis • Rat • Subventricular zone

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