Regulation of gastric H(+)-K(+)-ATPase by cAMP-dependent protein kinase.
A functional approach was utilized to isolate protein effectors from cAMP-stimulated rabbit gastric microsomes capable of stimulating H(+)-K(+)-ATPase activity. These studies have resulted in isolation of a cAMP-dependent protein kinase product from rabbit gastric microsomes which is capable of stimulating the proton pump of the parietal cell, H(+)-K(+)-ATPase, in inhibited gastric microsomes. This protein is membrane-bound and may be extracted from gastric microsomes only in the phosphorylated state. This phosphoprotein has at least 20 phosphorylation sites and produces enhancement of H(+)-K(+)-ATPase activity which equals that induced by the K+ ionophore, valinomycin. It would appear, therefore, that cAMP-mediated acid secretion involves phosphorylation of a membrane-bound cAMP-dependent protein kinase substrate in close proximity to the proton pump which produces K+ conductance and thereby controls the rate of acid secretion. The degree of phosphorylation of this protein is probably controlled by the activities of cAMP-dependent protein kinase and phosphoprotein phosphatase.
Sack
J
J
Department of Surgery, University of Alabama at Birmingham.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002850:Chromatography, Gel; D000242:Cyclic AMP / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D010750:Phosphoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D014634:Valinomycin / Q000494:pharmacology
D008565:Membrane Proteins; D010750:Phosphoproteins; D014634:Valinomycin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D017506:H(+)-K(+)-Exchanging ATPase