ArticleProceedings of the National Academy of Sciences of the United States of America1996
Identification of a second transmembrane protein tyrosine phosphatase, IA-2beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor of the 37-kDa tryptic fragment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus.Diabetes care · 2011Guideline
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- Phogrin Regulates High-Fat Diet-Induced Compensatory Pancreatic β-Cell Growth by Switching Binding Partners.Nutrients · 2024Article
- Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.Diabetes care · 2023Review
- Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.Clinical chemistry · 2023Article
- Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution.International journal of molecular sciences · 2022Article
- DNA methylation profiles in the blood of newborn term infants born to mothers with obesity.PloS one · 2022Article
- Insight into formation propensity of pseudocircular DNA G-hairpins.Nucleic acids research · 2021Article
- Cerebrospinal fluid proteomics implicates the granin family in Parkinson's disease.Scientific reports · 2020Article
- Birth and coming of age of islet autoantibodies.Clinical and experimental immunology · 2019Review
- Distinct genome-wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors.Cancer · 2019Article
- Regulation of CD4Frontiers in immunology · 2019Review
- Pathophysiologic changes in IA-2/IA-2β null mice are secondary to alterations in the secretion of hormones and neurotransmitters.Acta diabetologica · 2016Article
- PTPRN2 and PLCβ1 promote metastatic breast cancer cell migration through PI(4,5)P2-dependent actin remodeling.The EMBO journal · 2016Article
- Excitatory and Inhibitory Neurons in the Hippocampus Exhibit Molecularly Distinct Large Dense Core Vesicles.Frontiers in cellular neuroscience · 2016Article
- Peripheral blood methylation profiling of female Crohn's disease patients.Clinical epigenetics · 2016Article
- The minimal promoter region of the dense-core vesicle protein IA-2: transcriptional regulation by CREB.Acta diabetologica · 2015Article
- X-ray structure of the mature ectodomain of phogrin.Journal of structural and functional genomics · 2015Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A novel cDNA, IA-2beta, was isolated from a mouse neonatal brain library. The predicted protein sequence revealed an extracellular domain, a transmembrane region, and an intracellular domain. The intracellular domain is 376 amino acids long and 74% identical to the intracellular domain of IA-2, a major autoantigen in insulin-dependent diabetes mellitus (IDDM). A partial sequence of the extracellular domain of IA-2beta indicates that it differs substantially (only 26% identical) from that of IA-2. Both molecules are expressed in islets and brain tissue. Forty-six percent (23 of 50) of the IDDM sera but none of the sera from normal controls (0 of 50) immunoprecipitated the intracellular domain of IA-2beta. Competitive inhibition experiments showed that IDDM sera have autoantibodies that recognize both common and distinct determinants on IA-2 and IA-2beta. Many IDDM sera are known to immunoprecipitate 37-kDa and 40-kDa tryptic fragments from islet cells, but the identity of the precursor protein(s) has remained elusive. The current study shows that treatment of recombinant IA-2beta and IA-2 with trypsin yields a 37-kDa fragment and a 40-kDa fragment, respectively, and that these fragments can be immunoprecipitated with diabetic sera. Absorption of diabetic sera with unlabeled recombinant IA-2 or IA-2beta, prior to incubation with radiolabeled 37-kDa and 40-kDa tryptic fragments derived from insulinoma or glucagonoma cells, blocks the immunoprecipitation of both of these radiolabeled tryptic fragments. We conclude that IA-2beta and IA-2 are the precursors of the 37-kDa and 40-kDa islet cell autoantigens, respectively, and that both IA-2 and IA-2beta are major autoantigens in IDDM.
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