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

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

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Transforming growth factor β (TGF-β) causes growth arrest in epithelial cells and proliferation and morphological transformation in fibroblasts. Despite the ability of TGF-β to induce various cellular phenotypes, few discernible differences in TGF-β signaling between cell types have been reported, with the only well-characterized pathway (the Smad cascade) seemingly under identical control. We determined that TGF-β 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-β-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-β addition. Thus, PAK2 represents a novel Smad-independent pathway that differentiates TGF-β signaling in fibroblast (growth-stimulated) and epithelial cell (growth-inhibited) cultures.

Original languageEnglish (US)
Pages (from-to)8878-8889
Number of pages12
JournalMolecular and cellular biology
Issue number23
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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