title: Comprehensive identification of arginine methylation in primary T cells reveals regulatory roles in cell signalling.
abstract: 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.
authors: Laboratory of T cell signalling, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors: Vincent
authors: V
authors: Geoghegan
authors: Cell Signaling Technology Inc., Trask Lane, Danvers, Massachusetts 01923, USA.
authors: Ailan
authors: A
authors: Guo
authors: Central Proteomics Facility, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors: David
authors: D
authors: Trudgian
authors: Central Proteomics Facility, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors: Benjamin
authors: B
authors: Thomas
authors: Laboratory of T cell signalling, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors: Oreste
authors: O
authors: Acuto
mesh_terms: D001120:Arginine / Q000378:metabolism*; D002454:Cell Differentiation; D006801:Humans; D008213:Lymphocyte Activation; D013058:Mass Spectrometry; D008745:Methylation; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases