Relationship of the 37,000- and 40,000-Mr tryptic fragments of islet antigens in insulin-dependent diabetes to the protein tyrosine phosphatase-like molecule IA-2 (ICA512)

Payton, M. A. and Hawkes, C. J. and Christie, M. R. (1995) Relationship of the 37,000- and 40,000-Mr tryptic fragments of islet antigens in insulin-dependent diabetes to the protein tyrosine phosphatase-like molecule IA-2 (ICA512). Journal of Clinical Investigation, 96 (3). pp. 1506-1511. ISSN 0021-9738

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Abstract

Sera from patients with insulin-dependent diabetes immunoprecipitate 64,000-Mr proteins, distinct from glutamate decarboxylase, that are cleaved to 37,000- and 40,000-Mr fragments by trypsin. We investigated possible relationships between 37,000- or 40,000-Mr. fragments of antigen and the tyrosine phosphatase-like protein, IA-2 (ICA512). Antibodies from nondiabetic relatives bound differentially to 37,000- and 40,000-Mr fragments indicating presence of distinct epitopes. Precursors of these fragments could be separated on immobilized lectins, suggesting different carbohydrate content. Levels of antibodies to 40,000-Mr fragments were strongly associated with those to the intracellular domain of IA-2. Recombinant intracellular domain of IA-2 blocked binding of antibodies to 40,000-Mr fragments expressed by insulinoma cells and partially blocked binding to 37,000-A/r fragments. Furthermore, trypsinization of recombinant intracellular domain of IA-2 generated proteolytic fragments of identical Mr to the 40,000-Mr fragments of insulinoma antigen; 37,000-M2 fragments were not generated. Thus, 40,000-Mr fragments of islet autoantigen are derived from a protein similar or identical to the tyrosine phosphatase-like molecule, IA-2. The 37,000-Mr fragments are derived from a different, although related, protein.

Keywords:autoantigen, complementary dna, epitope, pancreas islet cell antibody, protein tyrosine phosphatase, trypsin, affinity chromatography, animal cell, antigen binding, article, blood sampling, cell line, controlled study, human, immunoprecipitation, insulin dependent diabetes mellitus, insulinoma, molecular cloning, nonhuman, priority journal, rat, Animal, Antigen-Antibody Reactions, Antigens, Base Sequence, Brain, Carbohydrates, Cloning, Molecular, Comparative Study, Diabetes Mellitus, Insulin-Dependent, DNA Primers, Family, Glutamate Decarboxylase, Islets of Langerhans, Lectins, Membrane Proteins, Molecular Sequence Data, Molecular Weight, Peptide Fragments, Polymerase Chain Reaction, Protein-Tyrosine-Phosphatase, Rats, Recombinant Proteins, Reference Values, Support, Non-U.S. Gov't, Trypsin
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18155
Deposited On:07 Aug 2015 15:39

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