Comprehensive identification of arginine methylation in primary T cells reveals regulatory roles in cell signalling

Nat Commun. 2015 Apr 7:6:6758. doi: 10.1038/ncomms7758.


The impact of protein arginine methylation on the regulation of immune functions is virtually unknown. Here, we apply a novel method—isomethionine methyl-SILAC—coupled with antibody-mediated arginine-methylated peptide enrichment to identify methylated peptides in human T cells by mass spectrometry. This approach allowed the identification of 2,502 arginine methylation sites from 1,257 tissue-specific and housekeeping proteins. We find that components of T cell antigen receptor signal machinery and several key transcription factors that regulate T cell fate determination are methylated on arginine. Moreover, we demonstrate changes in arginine methylation stoichiometry during cellular stimulation in a subset of proteins critical to T cell differentiation. Our data suggest that protein arginine methyltransferases exert key regulatory roles in T cell activation and differentiation, opening a new field of investigation in T cell biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arginine / metabolism*
  • Cell Differentiation*
  • Humans
  • Lymphocyte Activation*
  • Mass Spectrometry
  • Methylation
  • Protein Processing, Post-Translational
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / metabolism*
  • Transcription Factors / metabolism*


  • Receptors, Antigen, T-Cell
  • Transcription Factors
  • Arginine
  • Protein-Arginine N-Methyltransferases