Biochemical study on transcriptional regulation of gastric proton pump genes.

点击翻译按钮获取中文摘要

Gastric parietal cells have a characteristic morphology and secrete HCl into gastric lumen, synthesizing specific enzymes essential for the secretion. The genes for the gastric proton pump (H^+/K^+-ATPase) alpha and beta subunits have been shown to be transcribed and translated only in the parietal cell. The H^+/K^+-ATPase alpha and beta subunits are highly similar to those of the corresponding subunits of Na^+/K^+-ATPase. However, the nucleotide sequences in the control regions of the genes for the H^+/K^+-ATPase alpha and beta subunits have no apparent similarities with those of Na^+/K^+-ATPase subunits. The 5'-upstream regions of the rat and human H^+/K^+-ATPase alpha subunit genes are conserved, suggesting that the conserved regions may be important for the transcriptional regulation of the alpha subunit gene. We found that gastric mucosal nuclear protein(s) recognized a sequence motif (TAATCAGCTG)in the 5'-upstream regions of both the rat and human genes for the alpha subunit of H^+/K^+-ATPase. This gastric specific protein also bound to the motif (GATAGC) in the rat beta subunit gene. The consensus core sequence motif for the alpha and beta subunit is suggested to be [(G/C)PuPu(G/C)NGAT(A/T)PuPy]. cDNAs for the DNA binding proteins recognizing this sequence motif were cloned. We also cloned H2-histamine receptor and intrinsic factor genes and characterized their control regions. Human sera from autoimmune gastritis patients containing autoantibodies to gastric parietal cells were analyzed by immunological methods and we found that each patients sera contains a mixtures of autoantibodies recognizing different epitopes with variable contents.