胃粘膜プロトンポンプ遺伝子と転写調節

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タイトル別名
  • Genes for Gastric Proton Pump and Their Transcriptional Regulation
  • イ ネンマク プロトン ポンプ イデンシ ト テンシャ チョウセツ

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説明

The highly differentiated gastric parietal cell has a characteristic morphology and plays a specialized role in the hydrochloric acid secretion into the stomach lumen. The major enzyme in this system is an ATP-driven proton pump, the H+/K+-ATPase, which is responsible for proton translocation across the apical plasma membrane. The primary structures of the catalytic α and glycosylated β subunits, and their transmembrane topology are similar to those of the corresponding subunits of Na+/K+-ATPase, suggesting that the reaction mechanism of both ATPases would be essentially the same if not identical. Most of the positions of introns in the H+/K+-ATPase subunit genes are essentially the same as those in the corresponding Na+/K+-ATPase subunit gene. These findings suggest that the α and β subunit genes, respectively, of the two ATPases were derived from the common ancestors. We found that a DNA sequence motif, (G/C) PuPu (G/C) NGAT (A/T) PuPy, was located in the upstream regions of both α and β subunit genes from human and rat. This motif may be a binding site for a positive transcriptional regulator that functions specifically in the parietal cells. cDNA cloning and in situ hybridization demonstrated that novel zinc finger proteins (GATA-GT1 and GATA-GT2) are present in the gastric parietal cells. These proteins bind to the (G/C) PuPu (G/C) NGAT (A/T) PuPy motif. Furthermore, they activate the transcription of the reporter gene with the 5'-upstream region of the α or β subunit gene. These results suggest that gastric GATA DNA-binding proteins play important roles in transcriptional activation of H+/K+-ATPase genes in the parietal cells.

収録刊行物

  • 薬学雑誌

    薬学雑誌 116 (2), 91-105, 1996

    公益社団法人 日本薬学会

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