Methylation of Smad6 by protein arginine N-methyltransferase 1.
Signal transduction pathways utilize posttranslational modifications to regulate the activity of their components in a temporal-spatial and efficient fashion. Arginine methylation is one of the posttranslational modifications that can result in monomethylated-, asymmetric dimethylated- and/or symmetric dimethylated-arginine residues in proteins. Here we demonstrate that inhibitory-Smads (Smad6 and Smad7), but not receptor-regulated- (R-)Smads and the common-partner Smad4, can be methylated by protein arginine N-methyltransferase (PRMT)1. Using mass-spectrometric analysis, we found that PRMT1 dimethylates arginine(74) (Arg(74)) in mouse Smad6. PRMT1 interacts with the N-terminal domain of Smad6 in which Arg(74) residue is located. Assays examined so far have shown no significant differences between the functions of Smad6 and those of methylation-defective Smad6 (Smad6R74A). Both wild-type and Smad6R74A were equally efficient in blocking BMP-induced growth arrest upon their ectopic expression in HS-72 mouse B-cell hybridoma cells.
Inamitsu
Masako
M
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Itoh
Susumu
S
Hellman
Ulf
U
Ten Dijke
Peter
P
Kato
Mitsuyasu
M
D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D008745:Methylation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D051905:Smad6 Protein / Q000737:chemistry / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D050505:Mutant Proteins; D051905:Smad6 Protein; C497803:Smad6 protein, mouse; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases; D000409:Alanine