Transforming growth factor-β activation of phosphatidylinositol 3-kinase is independent of Smad2 and Smad3 and regulates fibroblast responses via p21-activated kinase-2

Mark C. Wilkes, Hugh Mitchell, Sumedha Gulati Penheiter, Jules J. Doré, Kaori Suzuki, Maryanne Edens, Deepak K. Sharma, Richard E. Pagano, Edward B. Leof

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) stimulates cellular proliferation and transformation to a myofibroblast phenotype in vivo and in a subset of fibroblast cell lines. As the Smad pathway is activated by TGF-β in essentially all cell types, it is unlikely to be the sole mediator of cell type-specific outcomes to TGF-β stimulation. In the current study, we determined that TGF-β receptor signaling activates phosphatidylinositol 3-kinase (PI3K) in several fibroblast but not epithelial cultures independently of Smad2 and Smad3. PI3K activation occurs in the presence of dominant-negative dynamin and is required for p21-activated kinase-2 kinase activity and the increased proliferation and morphologic change induced by TGF-β in vitro.

Original languageEnglish (US)
Pages (from-to)10431-10440
Number of pages10
JournalCancer research
Volume65
Issue number22
DOIs
StatePublished - Nov 15 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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