Protein kinase C delta is a substrate of tissue transglutaminase and a novel autoantigen in coeliac disease

Greg Byrne; Michael Freeley; Con Feighery; Alex Whelan; Aideen Long

doi:10.1016/j.clim.2013.01.007

Protein kinase C delta is a substrate of tissue transglutaminase and a novel autoantigen in coeliac disease

Greg Byrne, Michael Freeley, Con Feighery, Alex Whelan, Aideen Long

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1-8
Number of pages	8
Journal	Clinical Immunology
Volume	147
Issue number	1
DOIs	https://doi.org/10.1016/j.clim.2013.01.007
Publication status	Published - Apr 2013

Keywords

Autoantibodies
Coeliac disease
Protein kinase C delta
Tissue transglutaminase

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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.",

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AU - Byrne, Greg

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AU - Feighery, Con

AU - Whelan, Alex

AU - Long, Aideen

PY - 2013/4

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N2 - 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.

AB - 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.

KW - Autoantibodies

KW - Coeliac disease

KW - Protein kinase C delta

KW - Tissue transglutaminase

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Protein kinase C delta is a substrate of tissue transglutaminase and a novel autoantigen in coeliac disease

Abstract

Keywords

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