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.
journal_name
Diabetesjournal_title
Diabetesauthors
Hawkes CJ,Wasmeier C,Christie MR,Hutton JCdoi
10.2337/diab.45.9.1187subject
Has Abstractpub_date
1996-09-01 00:00:00pages
1187-92issue
9eissn
0012-1797issn
1939-327Xjournal_volume
45pub_type
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