title: Biochemical analysis of the arginine methylation of high molecular weight fibroblast growth factor-2.
abstract: The post-translational methylation of the N-terminally extended or high molecular weight (HMW) forms of fibroblast growth factor-2 (FGF-2) has been shown to affect the nuclear accumulation of the growth factor. In this study, we determined the extent and position of methyl groups in HMW FGF-2. Using mass spectrometry and amino acid sequence analysis, we have shown that the 22- and 22.5-kDa forms of HMW FGF-2 contain five dimethylated arginines located at positions -22, -24, -26, -36, and -38 using the methionine residue normally used to initiate the 18-kDa form as position 0. The 24-kDa form of HMW FGF-2 contains seven to eight dimethylated arginines located at positions -48, -50, and -52, in addition to positions -22, -24, -26, -36, and -38. In vitro methylation reactions demonstrate that the N-terminal extension of HMW FGF-2 acts as a specific substrate for yeast Hmt1p and human HRMT1L2 arginine methyltransferases. These findings indicate that HMW FGF-2, with the presence of five or more dimethylated Gly-Arg-Gly repeats, contains an RGG box-like domain, which may be important for protein-protein and/or protein-RNA interactions.
authors.affiliation: Department of Cell Biology, New York University Medical School, New York, New York 10013, USA. s-klein@ski.mskcc.org
authors.forename: S
authors.initials: S
authors.lastname: Klein
authors.forename: J A
authors.initials: JA
authors.lastname: Carroll
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: M F
authors.initials: MF
authors.lastname: Henry
authors.forename: P A
authors.initials: PA
authors.lastname: Henry
authors.forename: I E
authors.initials: IE
authors.lastname: Ortonowski
authors.forename: G
authors.initials: G
authors.lastname: Pintucci
authors.forename: R C
authors.initials: RC
authors.lastname: Beavis
authors.forename: W H
authors.initials: WH
authors.lastname: Burgess
authors.forename: D B
authors.initials: DB
authors.lastname: Rifkin
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein
chemical_list: D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D001120:Arginine