title: The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3.
abstract: 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.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, The University of Tokyo, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kunizaki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hamamoto
authors.forename: Fabio Pittella
authors.initials: FP
authors.lastname: Silva
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.forename: Masabumi
authors.initials: M
authors.lastname: Shibuya
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D008745:Methylation; D008954:Models, Biological; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011496:Protein Methyltransferases; D012694:Serine / Q000737:chemistry; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012694:Serine; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D008239:Lysine