RGD Reference Report - Alpha and beta subunits of the gastric H+/K(+)-ATPase are concordantly targeted by parietal cell autoantibodies associated with autoimmune gastritis. - Rat Genome Database

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Alpha and beta subunits of the gastric H+/K(+)-ATPase are concordantly targeted by parietal cell autoantibodies associated with autoimmune gastritis.

Authors: Callaghan, J M  Khan, M A  Alderuccio, F  van Driel, I R  Gleeson, P A  Toh, B H 
Citation: Callaghan JM, etal., Autoimmunity. 1993;16(4):289-95.
RGD ID: 14696746
Pubmed: PMID:7517707   (View Abstract at PubMed)

We have previously shown that parietal cell autoantibodies predominantly react with a 60-90 kDa gastric autoantigen, subsequently identified as the beta subunit of the gastric H+/K(+)-ATPase (EC 3.6.1.3) (proton pump) whereas Karlsson et al showed that these autoantibodies primarily target the 95 kDa alpha subunit of the pump. In view of these discordant results, we have reassessed the reactivity of parietal cell autoantibodies with the two subunits of the gastric H+/K(+)-ATPase. We show here that all 26 parietal cell autoantibody-positive sera immunoblot both subunits under appropriate, but mutually exclusive, conditions. Thus, reactivity of anti-parietal cell autoantibodies with the 95 kDa alpha subunit is optimal when the SDS-PAGE is carried out with samples which are reduced but not boiled. Whereas reactivity with the 60-90 kDa beta subunit is optimal with samples which are boiled but not reduced. Autoantibody reactivity with the beta subunit is critically dependent on the presence of a full complement of N-linked glycans since partially deglycosylated protein, and recombinant beta subunit expressed in COS cells, bearing high mannose N-glycans, failed to bind to the autoantibody. These studies also suggest that B cell auto-epitopes are located on the lumenal domain of the beta subunit. Reactivity of parietal cell autoantibodies with a bacterial fusion protein incorporating the catalytic cytoplasmic domain of the alpha subunit suggests the presence of auto-epitopes in this region of the molecule.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
autoimmune gastritis  IDA 14696746 RGD 
autoimmune gastritis  ISOATP4B (Homo sapiens)14696746; 14696746 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp4b  (ATPase H+/K+ transporting subunit beta)

Genes (Mus musculus)
Atp4b  (ATPase, H+/K+ exchanging, beta polypeptide)

Genes (Homo sapiens)
ATP4B  (ATPase H+/K+ transporting subunit beta)


Additional Information