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

137 Citations (Scopus)

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

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p21-Activated Kinases
Phosphatidylinositol 3-Kinase
Transforming Growth Factors
Fibroblasts
Dynamins
Myofibroblasts
Growth Factor Receptors
Phosphotransferases
Cell Proliferation
Phenotype
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Transforming growth factor-β activation of phosphatidylinositol 3-kinase is independent of Smad2 and Smad3 and regulates fibroblast responses via p21-activated kinase-2. / Wilkes, Mark C.; Mitchell, Hugh; Penheiter, Sumedha Gulati; Doré, Jules J.; Suzuki, Kaori; Edens, Maryanne; Sharma, Deepak K.; Pagano, Richard E.; Leof, Edward B.

In: Cancer Research, Vol. 65, No. 22, 15.11.2005, p. 10431-10440.

Research output: Contribution to journalArticle

Wilkes, Mark C. ; Mitchell, Hugh ; Penheiter, Sumedha Gulati ; Doré, Jules J. ; Suzuki, Kaori ; Edens, Maryanne ; Sharma, Deepak K. ; Pagano, Richard E. ; Leof, Edward B. / Transforming growth factor-β activation of phosphatidylinositol 3-kinase is independent of Smad2 and Smad3 and regulates fibroblast responses via p21-activated kinase-2. In: Cancer Research. 2005 ; Vol. 65, No. 22. pp. 10431-10440.
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