Cyclin-dependent kinase-3-mediated c-Jun phosphorylation at Ser63 and Ser73 enhances cell transformation.
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 NH(2)-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 Cl41 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.
Cho
Yong-Yeon
YY
The Hormel Institute, University of Minnesota, 801 16th Avenue Northeast, Austin, MN 55912, USA.
Tang
Faqing
F
Yao
Ke
K
Lu
Chengrong
C
Zhu
Feng
F
Zheng
Duo
D
Pugliese
Angelo
A
Bode
Ann M
AM
Dong
Zigang
Z
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D056849:Cyclin-Dependent Kinase 3; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection
D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D012694:Serine; D004815:Epidermal Growth Factor; C098776:CDK3 protein, human; C490914:Cdk3 protein, mouse; D056849:Cyclin-Dependent Kinase 3; D018844:Cyclin-Dependent Kinases