Roles of gastric GATA DNA-binding proteins.
The gastric H+/K(+)-ATPase is a P-type ATPase that is specifically expressed in gastric parietal cells and is responsible for acid secretion into the stomach. We have found one or more gastric mucosal nuclear proteins that recognize a sequence motif in the 5'-upstream regions of the H+/K(+)-ATPase alpha- and beta-subunit genes. This gastric motif, (G/C)PuPu(G/C)NGAT(A/T)PuPy, may be a binding site for a positive transcriptional regulator that functions specifically in parietal cells. We further demonstrated using cDNA cloning and in situ hybridization that novel zinc-finger proteins (GATA-GT1 and GATA-GT2) are present in the gastric parietal cells and bind to this motif. The proteins activate the transcription of the reporter gene with the 5'-upstream region of the H+/K(+)-ATPase beta-subunit gene. These results suggest that gastric GATA DNA-binding proteins have important roles in transcriptional activation of H+/K(+)-ATPase genes in the parietal cells.
Maeda
M
M
Laboratory of Biochemistry, Osaka University, Japan.
Kubo
K
K
Nishi
T
T
Futai
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D010766:Phosphorylation; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014018:Tissue Distribution; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016335:Zinc Fingers / Q000235:genetics
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D050993:GATA6 Transcription Factor; C084365:Gata4 protein, rat; C084364:Gata6 protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; D006180:Proton-Translocating ATPases