Cyclin-Dependent Kinase-3-Mediated c-Jun Phosphorylation at Ser63 and Ser73 Enhances Cell Transformation

被引：52

作者：

Cho, Yong-Yeon ^{[1
]}

Tang, Faqing ^{[1
]}

Yao, Ke ^{[1
]}

Lu, Chengrong ^{[1
]}

Zhu, Feng ^{[1
]}

Zheng, Duo ^{[1
]}

Pugliese, Angelo ^{[1
]}

Bode, Ann M. ^{[1
]}

Dong, Zigang ^{[1
]}

机构：

[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA

来源：

CANCER RESEARCH | 2009年 / 69卷 / 01期

关键词：

ACTIVATED PROTEIN-KINASES; EPIDERMAL-GROWTH-FACTOR; N-TERMINAL KINASE; TRANSCRIPTION FACTOR; AP-1; ACTIVITY; MAP KINASES; TRANSGENIC MICE; JB6; CELLS; HA-RAS; DOMAIN;

D O I：

10.1158/0008-5472.CAN-08-3125

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

c-Jun is a component of the activator protein-1 (AP-1) complex, which plays a crucial role in the regulation of gene expression, cell proliferation, and cell transformation, as well as cancer development. Herein, we found that cyclin-dependent kinase (Cdk)-3, but not Cdk2 or c-Jun NH2-terminal kinase, is a novel kinase of c-Jun induced by stimulation with growth factors such as epidermal growth factor (EGF). Cdk3 was shown to phosphorylate c-Jun at Ser63 and Ser73 in vitro and ex vivo. EGF-induced Cdk3 activation caused c-Jun phosphorylation at Ser63 and Ser73, resulting in increased AP-1 transactivation. Ectopic expression of Cdk3 resulted in anchorage-independent cell transformation of JB6 CI41 cells induced by EGF and foci formation stimulated by constitutively active Ras (Ras(G12V)), which was mediated by AP-1 in NIH3T3 cells. These results showed that the Cdk3/c-Jun signaling axis plays an important role in EGF-stimulated cell proliferation and cell transformation. [Cancer Res 2009;69(1):272-81]

引用

页码：272 / 281

页数：10

共 49 条

[1] THE JUN PROTO-ONCOGENE IS POSITIVELY AUTOREGULATED BY ITS PRODUCT, JUN/AP-1 [J].