Des-γ-carboxyl Prothrombin-promoted Vascular Endothelial Cell Proliferation and Migration
Autor: | Yasushi Shiratori, Shin Ichi Nishina, Yutaka Nakanishi, Tatsuya Fujikawa, Noriyuki Matsuo, Hidenori Shiraha, Shigetomi Tanaka, Naoki Ueda, Mayumi Suzuki, Kohsaku Sakaguchi, Nobuyuki Takaoka, Akinobu Takaki |
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Rok vydání: | 2007 |
Předmět: |
STAT3 Transcription Factor
Umbilical Veins MAP Kinase Signaling System Biology Biochemistry chemistry.chemical_compound Cell Movement Cell Line Tumor Humans Gene Silencing Phosphorylation Protein Precursors RNA Small Interfering Protein kinase A Molecular Biology Cells Cultured Cell Proliferation Phospholipase C gamma Cell growth Vascular endothelial cell proliferation Kinase insert domain receptor Janus Kinase 1 Cell Biology Cell biology Vascular endothelial growth factor B Vascular endothelial growth factor Vascular endothelial growth factor A chemistry Prothrombin Endothelium Vascular Signal transduction Biomarkers |
Zdroj: | Journal of Biological Chemistry. 282:8741-8748 |
ISSN: | 0021-9258 |
DOI: | 10.1074/jbc.m609358200 |
Popis: | Des-gamma-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma. Previously, we have demonstrated that DCP stimulates cell proliferation in hepatocellular carcinoma cell lines through Met-Janus kinase 1 signal transducer and activator of transcription 3 signaling pathway. In the present study, we demonstrated that DCP induces both cell proliferation and migration in human umbilical vein endothelial cells. DCP was found to bind with the kinase insert domain receptor (KDR), alternatively referred to as vascular endothelial growth factor receptor-2. Furthermore, DCP induced autophosphorylation of KDR and its downstream effector phospholipase C-gamma and mitogen-activated protein kinase (MAPK). To support these results, we showed that DCP-induced cell proliferation and cell migration were inhibited by KDR short interfering RNA, KDR kinase inhibitor, or MAPK inhibitor. In conclusion, these results indicate that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities. |
Databáze: | OpenAIRE |
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