Gastric Proton Pump (H⁺/K⁺-ATPase): Structure and Gene Regulation through GATA DNA-Binding Protein(s)

抄録

Progress in molecular biological studies on the gastric proton pump (H⁺/K⁺-ATPase) now enable us to discuss not only its subunit protein structures and catalysis but also the organizations of its subunit genes and their cell-specific transcription. The primary structures of the catalytic α and glycosylated β subunits are similar to those of the corresponding subunits of Na⁺/K⁺-ATPase. The residues located in the catalytic and cation binding sites have been proposed from the combined results of protein chemical studies and sequence comparisons of P-type cation transporting ATPases. Most of the positions of exon/ intron boundaries of the genes for the H⁺/K⁺- and Na⁺/K⁺-ATPase α and β subunits are conserved, suggesting that the a and β subunit genes, respectively, of the two ATPases were derived from common ancestors. In contrast to the Na⁺/K⁺-ATPase subunits, the H⁺/ K⁺-ATPase α and β subunits are expressed specifically in gastric parietal cells. Consistent with their cell-specific transcription, a gastric mucosal nuclear protein(s) was shown to recognize a sequence motif in the 5'-upstream regions of the H⁺/K⁺-ATPase α and β subunit genes. Furthermore, novel zinc finger proteins (GATA-GT1 and GATA-GT2) that bind to this motif were found in the gastric parietal cells. These proteins are likely to play important roles in transcriptional regulation of the gastric proton pump genes.