title: Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase.
abstract: Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)- p21Cip/WAF1 activation, and suppressed by the mitogenactivated protein kinase (MAPK) inhibitor PD98059 and p21Cip/WAF1 short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.
authors.affiliation: Department of Biochemistry, BK 21 Program, College of Medicine, Korea University, Seoul.
authors.forename: Gyung Ah
authors.initials: GA
authors.lastname: Jung
authors.forename: Bong Shik
authors.initials: BS
authors.lastname: Shin
authors.forename: Yeon Sue
authors.initials: YS
authors.lastname: Jang
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Sohn
authors.forename: Seon Rang
authors.initials: SR
authors.lastname: Woo
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Go
authors.initials: G
authors.lastname: Choi
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Bon Hong
authors.initials: BH
authors.lastname: Min
authors.forename: Kee Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Gil Hong
authors.initials: GH
authors.lastname: Park
mesh_terms: D000818:Animals; D001120:Arginine; D054337:Cell Dedifferentiation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D054736:Elongation Factor 2 Kinase / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008745:Methylation; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D058628:Myofibroblasts / Q000473:pathology; D041681:NIH 3T3 Cells; D011496:Protein Methyltransferases / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005419:Flavonoids; D034741:RNA, Small Interfering; D016222:Fibroblast Growth Factor 2; D001120:Arginine; D011496:Protein Methyltransferases; C570798:PRMT7 protein, mouse; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases; D054736:Elongation Factor 2 Kinase; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one