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Post-translational modification of proteins by deamidation or transamidation by tissue transglutaminase (tTG) has been suggested as a possible mechanism for the development of autoimmunity. Sequence analysis of protein kinase C delta (PKCδ) identified an amino acid motif that suggested the possibility that PKCδ was a glutamine substrate of tTG and MALDI-TOF analysis of synthesised peptides from PKCδ proved that this was the case. Polymerisation experiments using recombinant tTG and biotinylated hexapeptide substrate incorporation assays demonstrated that PKCδ is a substrate for tTG-mediated transamidation. Elevated levels of anti-PKCδ antibodies were detected in sera from patients with coeliac disease (pb0.0001) but not from patients with other autoimmune disorders. These data suggest that a subset of patients with coeliac disease produce autoantibodies against PKCδ and that this response may stem from a tTG–PKCδ substrate interaction.
Byrne, G. M., Freeley, M., Feighery, C., Whelan, A., Long, A., (2013) ''Protein Kinase C Delta is a Substrate of Tissue Transglutaminase and a Novel Autoantigen in Coeliac Disease'', Clinical Immunology, Volume 147, Issue 1, April 2013, Pages 1-8, ISSN 1521-6616, doi:10.1016/j.clim.2013.01.007