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
Rok vydání: 2007
Předmět:
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