Wilkes Mark C, Mitchell Hugh, Penheiter Sumedha Gulati, Doré Jules J, Suzuki Kaori, Edens Maryanne, Sharma Deepak K, Pagano Richard E, Leof Edward B
Department of Biochemistry and Molecular Biology, Thoracic Diseases Research Unit, and Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Cancer Res. 2005 Nov 15;65(22):10431-40. doi: 10.1158/0008-5472.CAN-05-1522.
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.
转化生长因子-β（TGF-β）在体内以及部分成纤维细胞系中可刺激细胞增殖并使其转变为肌成纤维细胞表型。由于在基本上所有细胞类型中，Smad信号通路都可被TGF-β激活，因此它不太可能是TGF-β刺激产生细胞类型特异性结果的唯一介质。在本研究中，我们确定TGF-β受体信号传导在几种成纤维细胞培养物中可激活磷脂酰肌醇3激酶（PI3K），但在上皮细胞培养物中则不然，且该激活过程不依赖于Smad2和Smad3。PI3K的激活发生在显性负性发动蛋白存在的情况下，并且是p21激活激酶-2激酶活性以及TGF-β在体外诱导的增殖增加和形态变化所必需的。
