title: Protein kinase C delta is a substrate of tissue transglutaminase and a novel autoantigen in coeliac disease.
abstract: 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 (p<0.0001) 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.
authors: School of Biological Sciences, Dublin Institute of Technology, Dublin 8, Ireland. Electronic address: greg.byrne@dit.ie.
authors: Greg
authors: G
authors: Byrne
authors: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland.
authors: Michael
authors: M
authors: Freeley
authors: Department of Immunology, St. James's Hospital & Trinity College Dublin, Dublin, Ireland.
authors: Con
authors: C
authors: Feighery
authors: Department of Immunology, St. James's Hospital & Trinity College Dublin, Dublin, Ireland.
authors: Alex
authors: A
authors: Whelan
authors: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland.
authors: Aideen
authors: A
authors: Long
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002446:Celiac Disease / Q000276:immunology* / Q000378:metabolism; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D005973:Glutamine / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051745:Protein Kinase C-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity; D011503:Transglutaminases / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D010455:Peptides; D011994:Recombinant Proteins; D005973:Glutamine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D051745:Protein Kinase C-delta; D019204:GTP-Binding Proteins