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

doi:10.1158/0008-5472.CAN-05-1522

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

Pulmonary and Critical Care Medicine

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149 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 language	English (US)
Pages (from-to)	10431-10440
Number of pages	10
Journal	Cancer research
Volume	65
Issue number	22
DOIs	https://doi.org/10.1158/0008-5472.CAN-05-1522
State	Published - Nov 15 2005

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-05-1522

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Wilkes, M. C., Mitchell, H., Penheiter, S. G., Doré, J. J., Suzuki, K., Edens, M., Sharma, D. K., Pagano, R. E., & Leof, E. B. (2005). Transforming growth factor-β activation of phosphatidylinositol 3-kinase is independent of Smad2 and Smad3 and regulates fibroblast responses via p21-activated kinase-2. Cancer research, 65(22), 10431-10440. https://doi.org/10.1158/0008-5472.CAN-05-1522

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 et al.
In: Cancer research, Vol. 65, No. 22, 15.11.2005, p. 10431-10440.

Research output: Contribution to journal › Article › peer-review

Wilkes, MC, Mitchell, H, Penheiter, SG, Doré, JJ, Suzuki, K, Edens, M, Sharma, DK, Pagano, RE & Leof, EB 2005, 'Transforming growth factor-β activation of phosphatidylinositol 3-kinase is independent of Smad2 and Smad3 and regulates fibroblast responses via p21-activated kinase-2', Cancer research, vol. 65, no. 22, pp. 10431-10440. https://doi.org/10.1158/0008-5472.CAN-05-1522

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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.",

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AU - Doré, Jules J.

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AU - Edens, Maryanne

AU - Sharma, Deepak K.

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AU - Leof, Edward B.

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AB - 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.

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

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