Exp Mol Med.  2011 Oct;43(10):550-560. 10.3858/emm.2011.43.10.061.

Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase

• Jung GA
• Shin BS
• Jang YS
• Sohn JB
• Woo SR
• Kim JE
• Choi G
• Lee KM
• Min BH
• Lee KH
• Park GH

• KMID: 1123367
• DOI: http://doi.org/10.3858/emm.2011.43.10.061

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)-p21(Cip/WAF1) activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and p21(Cip/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.

Keyword

cyclin-dependent kinase inhibitor p21; fibroblast growth factor 2; mitogen-activated protein kinases; N,N-dimethylarginine; peptide elongation factor 2; protein-arginine N-methyltransfe

MeSH Terms

Animals
Arginine
Cell Dedifferentiation
Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism
Elongation Factor 2 Kinase/*metabolism
Fibroblast Growth Factor 2/*metabolism
Fibroblasts/*metabolism/pathology
Flavonoids/pharmacology
MAP Kinase Signaling System/drug effects/genetics
Methylation
Mice
Mitogen-Activated Protein Kinases/antagonists & inhibitors
Myofibroblasts/pathology
NIH 3T3 Cells
Protein Methyltransferases/*metabolism
Protein-Arginine N-Methyltransferases/*metabolism
RNA, Small Interfering/genetics