Identification of the 37-kDa antigen in IDDM as a tyrosine phosphatase- like protein (phogrin) related to IA-2

Hawkes, C. J. and Wasmeier, C. and Christie, M. R. and Hutton, J. C. (1996) Identification of the 37-kDa antigen in IDDM as a tyrosine phosphatase- like protein (phogrin) related to IA-2. Diabetes, 45 (9). pp. 1187-1192. ISSN 0012-1797

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Item Type:Article
Item Status:Live Archive

Abstract

Antibodies to islet cell proteins detected as 37,000 and 40,000 M(r) tryptic fragments (37- and 40-kDa antigens) are strongly associated with progression to IDDM. The 40-kDa antigen has recently been identified as the tyrosine phosphatase-like protein IA-2 (ICA512) whereas the 37-kDa antigen has been suggested to be a different protein that has structural similarity to IA-2. A protein, phogrin, that has 80 amino acid sequence identity to IA- 2 in the cytoplasmic domain, has recently been cloned from an insulinoma cell cDNA library. In this study, we have investigated possible relationships between the 37-kDa antigen and phogrin. Antibodies to phogrin were detected in sera from patients with IDDM, and these antibodies were strongly correlated with the presence of antibodies to the 37-kDa antigen. Trypsin treatment of immunoprecipitated phogrin generated a 37,000 M(r) fragment. Recombinant phogrin was able to block autoantibody binding to the 37-kDa antigen but not to the 40-kDa antigen, and rabbit antibodies raised to different regions of phogrin depleted insulinoma cell extracts specifically of the 37-kDa antigen. These results demonstrate that the 37-kDa antigen in IDDM is indistinguishable from phogrin and show that two distinct tyrosine phosphatase-related proteins are major targets of the autoimmune response in the disease.

Keywords:antigen, trypsin, amino acid sequence, antigen antibody complex, antigen binding, antigen expression, article, binding affinity, clinical article, enzyme activity, human, human cell, immunoprecipitation, insulin dependent diabetes mellitus, insulinoma, molecular cloning, priority journal, protein analysis, Animals, Antibodies, Antigen-Antibody Reactions, Autoantibodies, Autoantigens, Cloning, Molecular, Cross Reactions, Diabetes Mellitus, Type 1, Islets of Langerhans, Membrane Glycoproteins, Membrane Proteins, Molecular Weight, Neoplasm Proteins, Nuclear Family, Pancreatic Neoplasms, Protein-Tyrosine-Phosphatase, Rabbits, Rats, Recombinant Proteins, Reference Values
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18151
Deposited On:31 Jul 2015 15:09

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