Disease relevance of Atp4b

• We describe a transgenic mouse model of metastatic gastric cancer initiated by expressing simian virus 40 large tumor antigen (SV40 TAg), under control of regulatory elements from the mouse Atp4b gene, in the progenitors of acid-producing parietal cells [1].
• Characterization of H+,K+-ATPase T cell epitopes in human autoimmune gastritis [2].

High impact information on Atp4b

• Parietal cells normally do not express endocrine or neural features, and Atp4b-Cre bitransgenic mice with a Cre reporter confirmed that the Atp4b regulatory elements are not active in gastric enteroendocrine cells [1].
• These phospholipid flippase activities were inhibited by 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile (SCH 28080) (IC50 = 0.14-0.25 microM), a specific K+-ATPase inhibitor of gastric H+,K+-ATPase rich in gastric vesicles [3].
• The positions at which introns interrupt the coding regions of the mouse H,K-ATPase beta subunit and mouse Na,K-ATPase (EC 3.6.1.37) beta 2 subunit genes are identical [4].
• By analyzing the segregation of restriction fragment length polymorphisms among recombinant inbred strains of mice, we localized the H,K-ATPase beta subunit gene to murine chromosome 8 [5].
• The identity of the cDNA was established by comparing the deduced amino acid sequence with sequences of cyanogen bromide fragments of the porcine H,K-ATPase beta subunit [5].

Biological context of Atp4b

• A bovine abomasum lambda gt11 cDNA library was screened with a monoclonal antibody raised against the rabbit H,K-ATPase beta subunit [5].
• Recent molecular biology experiments suggest that renal H+,K+-ATPase activity may be the product of several closely related P-type ATPases [6].
• We find that the activities of renal H+,K+-ATPases in situ are regulated by endocytosis, which is mediated by an endocytosis signal in the cytoplasmic tail of the gastric H+,K+-ATPase beta-subunit [7].
• Therefore, future studies will need to resolve these discrepancies by determining if a unique, yet undiscovered H+,K+-ATPase isoform exists in kidney, or if post-translational modifications of the alpha- and/or beta-subunits could account for these functional diversities [8].
• Ablation of parietal cells in another transgenic mouse model expressing the H,K-ATPase beta-subunit-1035 to +24/diphtheria toxin fragment A fusion gene also produces amplification of lineage precursors, and similar effects on zymogenic and pit cell census [9].

Anatomical context of Atp4b

• Immunogold labelling with alpha- and beta-subunit-specific antibodies showed that the gastric H+,K+-ATPase was localized to the membranes of this tubular system, which therefore represented the configuration of the secretory membrane in the cytoplasm of the unstimulated parietal cell [10].
• The identities of the H+,K+-ATPase isoforms that are normally subject to endocytic regulation and the nature of the participating epithelial cell machinery have yet to be established [7].

Associations of Atp4b with chemical compounds

• The H+,K+-ATPase inhibitor omeprazole is a highly effective gastric antisecretory agent, both in animals and man, with a long duration of action [11].
• Confocal microscopy revealed stimulation-induced translocation of H+,K+-ATPase from tubulovesicles towards the luminal pole of parietal cells, whereas distribution of KCNQ1 K+ channels did not change to the same extent [12].
• To reconcile these expressed sensitivities to those reported in vitro in isolated tubules and cells in culture, it would be necessary to invoke modification of the pharmacologic insensitivity of the colonic H+,K+-ATPase to Sch-28080 [8].
• We have identified a tyrosine-based signal in the cytoplasmic tail of the H,K-ATPase beta-subunit which appears to be required for this endocytosis [13].

References