Gastric proton pump (H+/K(+)-ATPase): structure and gene regulation through GATA DNA-binding protein(s).
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 alpha and glycosylated beta 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 alpha and beta subunits are conserved, suggesting that the alpha and beta subunit genes, respectively, of the two ATPases were derived from common ancestors. In contrast to the Na+/K(+)-ATPase subunits, the H+/K(+)-ATPase alpha and beta 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 alpha and beta 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.
Maeda
M
M
Department of Organic Chemistry and Biochemistry, Osaka University.
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D010766:Phosphorylation; D017494:Proton Pumps / Q000737:chemistry* / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D017494:Proton Pumps; D014157:Transcription Factors; D017506:H(+)-K(+)-Exchanging ATPase