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Cancer Research 67, 10759, November 15, 2007. doi: 10.1158/0008-5472.CAN-07-1132
© 2007 American Association for Cancer Research

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Molecular Biology, Pathobiology, and Genetics

The Lysine 831 of Vascular Endothelial Growth Factor Receptor 1 Is a Novel Target of Methylation by SMYD3

Masaki Kunizaki1,4, Ryuji Hamamoto1, Fabio Pittella Silva1, Kiyoshi Yamaguchi1, Takeshi Nagayasu4, Masabumi Shibuya3, Yusuke Nakamura1 and Yoichi Furukawa2

1 Laboratory of Molecular Medicine, Human Genome Center and 2 Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo; 3 Department of Molecular Oncology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan and 4 Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Requests for reprints: Yoichi Furukawa, Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-5449-5373; Fax: 81-3-5449-5124; E-mail: furukawa{at}ims.u-tokyo.ac.jp.

We previously identified SMYD3 as a histone methyltransferase and showed that its expression was elevated in colorectal, hepatocellular, and breast carcinomas. In the investigation of methyltransferase activity of SMYD3, we have found that vascular endothelial growth factor receptor 1 (VEGFR1) was also methylated by SMYD3. We further identified the methylated residue at VEGFR1 lysine 831, which is located in the kinase domain and is conserved among VEGFR1 orthologues. We also found that the lysine is followed by serine, which is conserved among some of the methylation targets of histone methyltransferases. Furthermore, methylation of VEGFR1 enhanced its kinase activity in cells. These data should be helpful for the profound understanding of the biological role of SMYD3 and regulatory mechanisms of VEGFR1. Additionally our finding may facilitate the development of strategies that may inhibit the progression of cancer cells. [Cancer Res 2007;67(22):10759–65]




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Copyright © 2007 by the American Association for Cancer Research.