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Mol. Cell. Biol. 23 (23): 8878-8889

Copyright © 2003 by the American Society for Microbiology. All rights reserved.

Cell-Type-Specific Activation of PAK2 by Transforming Growth Factor ß Independent of Smad2 and Smad3

Mark C. Wilkes, Stephen J. Murphy, Nandor Garamszegi, and Edward B. Leof*

Department of Biochemistry and Molecular Biology, Thoracic Diseases Research Unit, and Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester Minnesota 55905

Received for publication 8 May 2003. Revision received 10 June 2003. Accepted for publication 21 August 2003.

Abstract: Transforming growth factor ß (TGF-ß) causes growth arrest in epithelial cells and proliferation and morphological transformation in fibroblasts. Despite the ability of TGF-ß to induce various cellular phenotypes, few discernible differences in TGF-ß signaling between cell types have been reported, with the only well-characterized pathway (the Smad cascade) seemingly under identical control. We determined that TGF-ß receptor signaling activates the STE20 homolog PAK2 in mammalian cells. PAK2 activation occurs in fibroblast but not epithelial cell cultures and is independent of Smad2 and/or Smad3. Furthermore, we show that TGF-ß-stimulated PAK2 activity is regulated by Rac1 and Cdc42 and dominant negative PAK2 or morpholino antisense oligonucleotides to PAK2 prevent the morphological alteration observed following TGF-ß addition. Thus, PAK2 represents a novel Smad-independent pathway that differentiates TGF-ß signaling in fibroblast (growth-stimulated) and epithelial cell (growth-inhibited) cultures.

* Corresponding author. Mailing address: Stabile 858, Mayo Clinic, Rochester, MN 55905. Phone: (507) 284-5717. Fax: (507) 284-4521. E-mail: leof.edward{at}

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