Evidence map›Paper›PMID 9100223›Full record

ArticleMolecular medicine (Cambridge, Mass.)1997

An islet-cell protein tyrosine phosphatase is a likely precursor to the 37-kDa autoantigen in type 1 diabetes: human and macaque sequences, tissue distribution, unique and shared epitopes, and predictive autoantibodies.

J LaGasse, L Jelinek, S Sexson, C Lofton-Day, J Breininger, P Sheppard, W Kindsvogel, W A Hagopian

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Article in Molecular medicine (Cambridge, Mass.), 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.8field-weighted citation impact, top 28% of its field
1 · What the graph read from it

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3 · Its place in the literature

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2 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

J LaGasseDepartment of Medicine, University of Washington, Seattle 98195, USA.
L Jelinek
S Sexson
C Lofton-Day
J Breininger
P Sheppard
W Kindsvogel
W A Hagopian
Seattle University · USUniversity of Washington · US

Funding

NCRR NIH HHS RR00037NCRR NIH HHS RR00166NIDDK NIH HHS DK17047
6 · The paper itself

Abstract

backgroundWe sought to identify novel islet-cell autoantigens to better understand the pathogenesis, prediction, and immunotherapy of type 1 diabetes. MATERIALS AND

methodsMacaque and human islet cDNA libraries expressed in mammalian cells were screened with human diabetes sera. A positive clone was sequenced directly and after 5' rapid amplification of cDNA ends (RACE). Northern blotting and in situ hybridization revealed the tissue distribution of the corresponding protein. Antigen, expressed by in vitro translation, and tryptic peptides were analyzed by SDS-PAGE. For the immunoprecipitations, 183 diabetic, 60 prediabetic, and 91 control sera were used. Truncated antigens were used in immunoprecipitations for epitope mapping. Recombinant antigen expressed in transfected fibroblasts was used in competition assays.

resultsSequencing yielded an 111-kDa, 1,013 amino acid, transmembrane protein (M1851) containing consensus protein tyrosine phosphatase (PTPase) sequence. M1851 was 77% identical in the intracellular domain, but only 31% identical extracellularly, to the islet-cell autoantigen ICA512. mRNA localized to brain, prostate, pancreatic islets, and adrenal medulla. After limited trypsinization, the in vitro translated antigen was 37 kDa. M1851 was recognized by 47% of prediabetes sera, 31% of new diabetes sera, but only 1% of healthy controls. Only 1/73 sera binding M1851 failed to bind ICA512, whereas 42/114 binding ICA512 did not bind M1851. M1851 reactivity was not fully displaced by ICA512 in 24/49 sera. Removing the C-terminal 27, 80, or 160 amino acids of M1851 decreased reactivity by 70%, 90%, and 100%, respectively.

conclusionsThis new islet-cell PTPase is likely to be the precursor to the 37-kDa tryptic fragment antigen. It is structurally related to ICA512 but has distinct diabetes autoantibody epitopes located at the C terminus.

Indexed as

Amino Acid SequenceAnimalsAutoantibodiesAutoantigensBase SequenceCloning, MolecularCOS CellsDiabetes Mellitus, Type 1Epitope MappingHumansIslets of LangerhansMacaca nemestrinaMolecular Sequence DataProtein PrecursorsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine PhosphatasesAutoantibodiesAutoantigensislet 37k antigenProtein PrecursorsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatases

Identifiers

PMID9100223
PMCPMC2230046
OpenAlexW22206575

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.