Multimerization of expressed protein-arginine methyltransferases during the growth and differentiation of rat liver

Biochim Biophys Acta. 2005 May 25;1723(1-3):240-7. doi: 10.1016/j.bbagen.2005.02.015. Epub 2005 Mar 17.

Abstract

Protein-arginine methylation is a posttranslational modification which yields monomethyl and dimethyl (asymmetric or symmetric) arginines in proteins. We investigated the expressions of PRMT1 and PRMT5 in relation to their catalytic activities in rat liver during growth and differentiation as well as in the pancreas. Western immunoblot analysis revealed that both PRMT1 and PRMT5 proteins were expressed in the cytosol of liver and pancreas with molecular mass of about 42 kDa and 72 kDa, respectively. However, on molecular sieve chromatography, the enzyme activities were eluted at about 500 kDa for PRMT5 and 440 kDa for PRMT1, indicating that the multimer complex of these expressed monomers were catalytically active. While the 500 kDa complex methylated predominantly myelin basic protein (MBP), the 440 kDa complex methylated hnRNP A1 protein. In fetal rat liver, the amount of expressed 42 kDa PRMT1 protein and the enzyme activity to methylate hnRNPA1 protein were 2- to 3-fold and 4- to 5-fold higher, respectively, than those of post-natal livers. While the 72 kDa PRMT5 protein was consistently expressed, its activity varied only about 2-fold. However, PRMT5 to methylate MBP showed one distinct peak at around the 20th day post-natal. Furthermore, while the PRMT1 enzyme activity increased more than 10-fold after 3 days of 70% partial hepatectomy, the amount of expressed PRMT1 protein was only about 3.2-fold higher than the control livers. In summary, we observed that PRMTs are catalytically active only in the form of multimers, but not as a dimer or tetramer of the expressed subunit. Furthermore, the amount of expressed PRMT protein, determined by Western immunoblot, did not correlate with the amount of their catalytic activity, and thus, some uncharacterized additional factor(s) may multimerize PRMTs to express catalytic activities in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalysis
  • Cell Differentiation
  • Liver / embryology
  • Liver / enzymology*
  • Liver / growth & development
  • Liver Regeneration
  • Male
  • Molecular Weight
  • Protein-Arginine N-Methyltransferases / chemistry*
  • Protein-Arginine N-Methyltransferases / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Protein-Arginine N-Methyltransferases