Altered regulation of Src tyrosine kinase by transforming growth factor β1 in a human hepatoma cell line

被引：18

作者：

Fukuda, K ^{[1
]}

Kawata, S ^{[1
]}

Tamura, S ^{[1
]}

Matsuda, Y ^{[1
]}

Inui, Y ^{[1
]}

Igura, T ^{[1
]}

Inoue, S ^{[1
]}

Kudara, T ^{[1
]}

Matsuzawa, Y ^{[1
]}

机构：

[1] Osaka Univ, Sch Med, Dept Internal Med 2, Suita, Osaka 565, Japan

来源：

HEPATOLOGY | 1998年 / 28卷 / 03期

关键词：

D O I：

10.1002/hep.510280329

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Transforming growth factor ps (TGF-beta s) are the potent growth inhibitors for various cell types. Certain transformed cells, however, show poor response to TGF-beta induced growth inhibition, which contributes to their uncontrolled proliferation. Recently, we have reported that TGF-beta(1) induces degradation of activated Src tyrosine kinase in rat fibroblasts, To elucidate the alteration in TGF-beta(1) signaling pathway in turner cells that cannot respond to the cytokine, we compared the effects of TGF-beta(1) on Src kinase in two human hepatoma cell lints, TGF-beta(1)-insensitive Mahlavu cells and TGF-beta(1)-sensitive HepG2 cells, TGF-beta(1) decreased Src kinase activity in HepG2 cells, but increased cellular Src levels and Src kinase activity in Mahlavu cells. Go-incubation of Mahlavu cells with TGF-beta 1 and 12-O-tetradecanoyl phorbol 13-acetate (TPA) decreased Src protein levels and Src kinase activity, inducing TGF-beta(1) sensitivity. TGF-beta(1) induced tyrosine dephosphorylation of Ras guanosine triphosphatase-activating protein (Ras-GAP) and Ras inactivation in HepG2 cells, but induced Ras-GAP phosphorylation and Ras activation in Mahlavu cells. The Src kinase inhibitor abolished the increase of Src kinase activity in TGF-beta(1)-treated Mahlavu cells, and induced TGF-beta(1) sensitivity. These findings suggest that regulation of Src kinase by TGF-beta(1) is altered in Mahlavu cells. The altered regulation of Src may contribute to TGF-beta(1) insensitivity in this cell line, at least in part through activation of Ras.

引用

页码：796 / 804

页数：9

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