Abstract
Des-γ-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-γ 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.
| Original language | English |
|---|---|
| Pages (from-to) | 8741-8748 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 282 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Mar 23 2007 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Des-γ-carboxyl prothrombin-promoted vascular endothelial cell proliferation and migration. / Fujikawa, Tatsuya; Shiraha, Hidenori; Ueda, Naoki; Takaoka, Nobuyuki; Nakanishi, Yutaka; Matsuo, Noriyuki; Tanaka, Shigetomi; Nishina, Shin Ichi; Suzuki, Mayumi; Takaki, Akinobu; Sakaguchi, Kohsaku; Shiratori, Yasushi.
In: Journal of Biological Chemistry, Vol. 282, No. 12, 23.03.2007, p. 8741-8748.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Des-γ-carboxyl prothrombin-promoted vascular endothelial cell proliferation and migration
AU - Fujikawa, Tatsuya
AU - Shiraha, Hidenori
AU - Ueda, Naoki
AU - Takaoka, Nobuyuki
AU - Nakanishi, Yutaka
AU - Matsuo, Noriyuki
AU - Tanaka, Shigetomi
AU - Nishina, Shin Ichi
AU - Suzuki, Mayumi
AU - Takaki, Akinobu
AU - Sakaguchi, Kohsaku
AU - Shiratori, Yasushi
PY - 2007/3/23
Y1 - 2007/3/23
N2 - Des-γ-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-γ 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.
AB - Des-γ-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-γ 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.
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U2 - 10.1074/jbc.M609358200
DO - 10.1074/jbc.M609358200
M3 - Article
VL - 282
SP - 8741
EP - 8748
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 12
ER -