The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a β subunit of the gastric H+/K+-ATPase (proton pump)

B. H. Toh, P. A. Gleeson, R. J. Simpson, R. L. Moritz, J. M. Callaghan, I. Goldkorn, C. M. Jones, T. M. Martinelli, F. T. Mu, D. C. Humphris, J. M. Pettitt, Y. Mori, T. Masuda, P. Sobieszczuk, J. Weinstock, T. Mantamadiotis, G. S. Baldwin

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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 languageEnglish
Pages (from-to)6418-6422
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number16
DOIs
Publication statusPublished - 5 Sep 1990

Keywords

  • acid secretion
  • organ-specific autoimmunity
  • pernicious anemia

Cite this

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. / The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a β subunit of the gastric H+/K+-ATPase (proton pump). In: Proceedings of the National Academy of Sciences of the United States of America. 1990 ; Vol. 87, No. 16. pp. 6418-6422.
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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.",
keywords = "acid secretion, organ-specific autoimmunity, pernicious anemia",
author = "Toh, {B. H.} and Gleeson, {P. A.} and Simpson, {R. J.} and Moritz, {R. L.} and Callaghan, {J. M.} and I. Goldkorn and Jones, {C. M.} and Martinelli, {T. M.} and Mu, {F. T.} and Humphris, {D. C.} and Pettitt, {J. M.} and Y. Mori and T. Masuda and P. Sobieszczuk and J. Weinstock and T. Mantamadiotis and Baldwin, {G. S.}",
year = "1990",
month = "9",
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doi = "10.1073/pnas.87.16.6418",
language = "English",
volume = "87",
pages = "6418--6422",
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Toh, BH, Gleeson, PA, Simpson, RJ, Moritz, RL, Callaghan, JM, Goldkorn, I, Jones, CM, Martinelli, TM, Mu, FT, Humphris, DC, Pettitt, JM, Mori, Y, Masuda, T, Sobieszczuk, P, Weinstock, J, Mantamadiotis, T & Baldwin, GS 1990, 'The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a β subunit of the gastric H+/K+-ATPase (proton pump)', Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 16, pp. 6418-6422. https://doi.org/10.1073/pnas.87.16.6418

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 journalArticleResearchpeer-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

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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

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