Abstract
Autoantibodies in the sera of patients with pernicious anemia recognize, in addition to the α subunit of the gastric H+/K+-ATPase, an abundant gastric microsomal glycoprotein of apparent M(r) 60,000-90,000. Herein we have colocalized the glycoprotein and the α subunit of the gastric H+/K+-ATPase to the tubulovesicular membranes of the parietal cell by immunogold electron microscopy. Moreover, the glycoprotein and the α subunit were coimmunoprecipitated, and copurified by immunoaffinity chromatography, with an anti-glycoprotein monoclonal antibody. The pig glycoprotein was purified by chromatography on tomato lectin-Sepharose, and five tryptic peptides from the purified glycoprotein were partially sequenced. The complete amino acid sequence, deduced from the nucleotide sequence of overlapping cDNA clones, showed 33% similarity to the sequence of the β subunit of the pig kidney Na+/K+-ATPase. We therefore propose that the 60- to 90-kDa glycoprotein autoantigen is the β subunit of the gastric H+/K+-ATPase and that the α and β subunits of the proton pump are major targets for autoimmunization in autoimmune gastritis.
| Original language | English |
|---|---|
| Pages (from-to) | 6418-6422 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 87 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - 5 Sep 1990 |
Keywords
- acid secretion
- organ-specific autoimmunity
- pernicious anemia
Cite this
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The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a β subunit of the gastric H+/K+-ATPase (proton pump). / Toh, B. H.; Gleeson, P. A.; Simpson, R. J.; Moritz, R. L.; Callaghan, J. M.; Goldkorn, I.; Jones, C. M.; Martinelli, T. M.; Mu, F. T.; Humphris, D. C.; Pettitt, J. M.; Mori, Y.; Masuda, T.; Sobieszczuk, P.; Weinstock, J.; Mantamadiotis, T.; Baldwin, G. S.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 16, 05.09.1990, p. 6418-6422.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a β subunit of the gastric H+/K+-ATPase (proton pump)
AU - Toh, B. H.
AU - Gleeson, P. A.
AU - Simpson, R. J.
AU - Moritz, R. L.
AU - Callaghan, J. M.
AU - Goldkorn, I.
AU - Jones, C. M.
AU - Martinelli, T. M.
AU - Mu, F. T.
AU - Humphris, D. C.
AU - Pettitt, J. M.
AU - Mori, Y.
AU - Masuda, T.
AU - Sobieszczuk, P.
AU - Weinstock, J.
AU - Mantamadiotis, T.
AU - Baldwin, G. S.
PY - 1990/9/5
Y1 - 1990/9/5
N2 - Autoantibodies in the sera of patients with pernicious anemia recognize, in addition to the α subunit of the gastric H+/K+-ATPase, an abundant gastric microsomal glycoprotein of apparent M(r) 60,000-90,000. Herein we have colocalized the glycoprotein and the α subunit of the gastric H+/K+-ATPase to the tubulovesicular membranes of the parietal cell by immunogold electron microscopy. Moreover, the glycoprotein and the α subunit were coimmunoprecipitated, and copurified by immunoaffinity chromatography, with an anti-glycoprotein monoclonal antibody. The pig glycoprotein was purified by chromatography on tomato lectin-Sepharose, and five tryptic peptides from the purified glycoprotein were partially sequenced. The complete amino acid sequence, deduced from the nucleotide sequence of overlapping cDNA clones, showed 33% similarity to the sequence of the β subunit of the pig kidney Na+/K+-ATPase. We therefore propose that the 60- to 90-kDa glycoprotein autoantigen is the β subunit of the gastric H+/K+-ATPase and that the α and β subunits of the proton pump are major targets for autoimmunization in autoimmune gastritis.
AB - Autoantibodies in the sera of patients with pernicious anemia recognize, in addition to the α subunit of the gastric H+/K+-ATPase, an abundant gastric microsomal glycoprotein of apparent M(r) 60,000-90,000. Herein we have colocalized the glycoprotein and the α subunit of the gastric H+/K+-ATPase to the tubulovesicular membranes of the parietal cell by immunogold electron microscopy. Moreover, the glycoprotein and the α subunit were coimmunoprecipitated, and copurified by immunoaffinity chromatography, with an anti-glycoprotein monoclonal antibody. The pig glycoprotein was purified by chromatography on tomato lectin-Sepharose, and five tryptic peptides from the purified glycoprotein were partially sequenced. The complete amino acid sequence, deduced from the nucleotide sequence of overlapping cDNA clones, showed 33% similarity to the sequence of the β subunit of the pig kidney Na+/K+-ATPase. We therefore propose that the 60- to 90-kDa glycoprotein autoantigen is the β subunit of the gastric H+/K+-ATPase and that the α and β subunits of the proton pump are major targets for autoimmunization in autoimmune gastritis.
KW - acid secretion
KW - organ-specific autoimmunity
KW - pernicious anemia
UR - http://www.scopus.com/inward/record.url?scp=0025142477&partnerID=8YFLogxK
U2 - 10.1073/pnas.87.16.6418
DO - 10.1073/pnas.87.16.6418
M3 - Article
VL - 87
SP - 6418
EP - 6422
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 16
ER -