A TYROSINE-BASED SIGNAL TARGETS H K-ATPASE TO A REGULATED COMPARTMENTAND IS REQUIRED FOR THE CESSATION OF GASTRIC-ACID SECRETION/

Gastric acid secretion is mediated by the H/K-ATPase of parietal cells . Activation of acid secretion involves insertion of H/K-ATPase into t he parietal cell plasmalemma, while its cessation is associated with r einternalization of the H/K-ATPase into an intracellular storage compa rtment The cytoplasmic tail of the H/K-ATPase beta subunit includes a four residue sequence homologous to tyrosine-based endocytosis signals . We generated transgenic mice expressing H/K-ATPase beta subunit in w hich this motif's tyrosine residue is mutated to alanine. Gastric glan ds from animals expressing mutant beta subunit constitutively secrete acid and continuously express H/K-ATPase at their cell surfaces. Thus, the beta subunit's tyrosine-based signal is required for the internal ization of H/K-ATPase and for the termination of acid secretion. As a consequence of chronic hyperacidity, the mice develop gastric ulcers a nd a hypertrophic gastropathy resembling Menetrier's disease.