School of Chemistry, University of Sydney, Sydney, NSW, 2006, Australia.
Instituto de Química y Fisicoquímica Biológica (IQUIFIB), CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
J Membr Biol. 2024 Apr;257(1-2):79-89. doi: 10.1007/s00232-024-00310-7. Epub 2024 Mar 4.
The gastric H,K-ATPase is an integral membrane protein which derives energy from the hydrolysis of ATP to transport H ions from the parietal cells of the gastric mucosa into the stomach in exchange for K ions. It is responsible for the acidic environment of the stomach, which is essential for digestion. Acid secretion is regulated by the recruitment of the H,K-ATPase from intracellular stores into the plasma membrane on the ingestion of food. The similar amino acid sequences of the lysine-rich N-termini α-subunits of the H,K- and Na,K-ATPases, suggests similar acute regulation mechanisms, specifically, an electrostatic switch mechanism involving an interaction of the N-terminal tail with the surface of the surrounding membrane and a modulation of the interaction via regulatory phosphorylation by protein kinases. From a consideration of sequence alignment of the H,K-ATPase and an analysis of its coevolution with protein kinase C and kinases of the Src family, the evidence points towards a phosphorylation of tyrosine-7 of the N-terminus by either Lck or Yes in all vertebrates except cartilaginous fish. The results obtained will guide and focus future experimental research.
胃 H,K-ATPase 是一种整合膜蛋白，它从 ATP 的水解中获取能量，将 H 离子从胃黏膜壁细胞中运输到胃中，以交换 K 离子。它负责胃的酸性环境，这对于消化是必不可少的。酸分泌受食物摄入时 H,K-ATPase 从细胞内储存库募集到质膜的调节。H,K- 和 Na,K-ATPase 的富含赖氨酸的 N 端 α 亚基的相似氨基酸序列表明存在相似的急性调节机制，具体而言，涉及 N 端尾部与周围膜表面相互作用的静电开关机制，以及通过蛋白激酶的调节磷酸化来调节相互作用。从 H,K-ATPase 的序列比对考虑，以及与蛋白激酶 C 和 Src 家族激酶的共进化分析，证据表明在除软骨鱼以外的所有脊椎动物中，N 端酪氨酸-7 由 Lck 或 Yes 磷酸化。所得结果将指导和集中未来的实验研究。
