title: Association of protein kinase A with AKAP150 facilitates pepsinogen secretion from gastric chief cells.
abstract: Cross talk between signal transduction pathways augments pepsinogen secretion from gastric chief cells. A-kinase anchoring proteins (AKAPs) associate with regulatory subunits of protein kinase A (PKA), protein kinase C (PKC), and protein phosphatase 2B (PP2B) and localize this protein complex to specific cell compartments. We determined whether an AKAP-signaling protein complex exists in chief cells and whether this modulates secretion. In Western blots, we identified AKAP150, a rodent homologue of human AKAP79 that coimmunoprecipitates with PKA, PKC, and actin. The association of PKA and PP2B was demonstrated by affinity chromatography. Confocal microscopy revealed colocalized staining at the cell periphery for AKAP150 and PKC. Ht31, a peptide that competitively displaces PKA from the AKAP complex, but not Ht31P, a control peptide, inhibited 8-Br-cAMP-induced pepsinogen secretion. Ht31 did not inhibit secretion that was stimulated by agents whose actions are mediated by PKC and/or calcium. However, Ht31, but not Ht31P, inhibited carbachol- and A23187-stimulated augmentation of secretion from cells preincubated with cholera toxin. These data suggest the existence in chief cells of a protein complex that includes AKAP150, PKA, PKC, and PP2B. Disruption of the AKAP-PKA linkage impairs cAMP-mediated pepsinogen secretion and cross talk between signaling pathways.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA.
authors.forename: G
authors.initials: G
authors.lastname: Xie
authors.forename: J P
authors.initials: JP
authors.lastname: Raufman
mesh_terms: D054758:A Kinase Anchor Proteins; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D019872:Chief Cells, Gastric / Q000187:drug effects / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D015151:Immunoblotting; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D020116:Pepsinogen A / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: D054758:A Kinase Anchor Proteins; C487775:AKAP5 protein, human; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D007476:Ionophores; D010455:Peptides; D000001:Calcimycin; D002217:Carbachol; D020116:Pepsinogen A; D002772:Cholera Toxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C