Des-γ-carboxyl prothrombin-promoted vascular endothelial cell proliferation and migration

Tatsuya Fujikawa, Hidenori Shiraha, Naoki Ueda, Nobuyuki Takaoka, Yutaka Nakanishi, Noriyuki Matsuo, Shigetomi Tanaka, Shin Ichi Nishina, Mayumi Suzuki, Akinobu Takaki, Kohsaku Sakaguchi, Yasushi Shiratori

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46 Citations (Scopus)

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 languageEnglish
Pages (from-to)8741-8748
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number12
DOIs
Publication statusPublished - Mar 23 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Fujikawa, T., Shiraha, H., Ueda, N., Takaoka, N., Nakanishi, Y., Matsuo, N., Tanaka, S., Nishina, S. I., Suzuki, M., Takaki, A., Sakaguchi, K., & Shiratori, Y. (2007). Des-γ-carboxyl prothrombin-promoted vascular endothelial cell proliferation and migration. Journal of Biological Chemistry, 282(12), 8741-8748. https://doi.org/10.1074/jbc.M609358200