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

被引：175

作者：

Wilkes, MC

Mitchell, H

Penheiter, SG

Doré, JJ

Suzuki, K

Edens, M

Sharma, DK

Pagano, RE

Leof, EB

机构：

[1] Mayo Clin, Ctr Canc, Rochester, MN 55905 USA

[2] Mayo Clin & Mayo Fdn, Thorac Dis Res Unit, Dept Biochem & Mol Biol, Rochester, MN 55905 USA

[3] Mayo Clin, Coll Med, Ctr Canc, Rochester, MN USA

[4] Mem Univ Newfoundland, Fac Med, Div Basic Med Sci, St John, NF A1B 3V6, Canada

来源：

CANCER RESEARCH | 2005年 / 65卷 / 22期

关键词：

D O I：

10.1158/0008-5472.CAN-05-1522

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Transforming growth factor-beta (TGF-beta) 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-beta in essentially all cell types, it is unlikely to be the sole mediator of cell type-specific outcomes to TGF-beta stimulation. In the current study, we determined that TGF-beta 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-beta in vitro.

引用

页码：10431 / 10440

页数：10

共 55 条

[1] Phosphatidylinositol 3-kinase function is required for transforming growth factor β-mediated epithelial to mesenchymal transition and cell migration [J].