Abstract
The isoform of protein kinase C responsible for the inhibition of histamine-stimulated adenylate cyclase by the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), has been investigated in a particulate fraction prepared from the human gastric cancer cell line HGT-1. Theα and∈ isoforms of protein kinase C were detected in HGT-1 cells and in a 40,000 × g particulate fraction by immunoblotting procedures. The inhibitory effect of TPA on histamine-stimulated adenylate cyclase was enhanced by the presence of Ca2+, but decreased in a concentrationdependent manner by anti-peptide antibody to protein kinase Cα, but not to protein kinase C∈. Addition of Ca2+ and TPA to the 40,000 × g particulate fraction stimulated the phosphorylation of the protein kinase C substrate myelin basic peptide 4–14. Protein kinase Cα is probably the isoform responsible for inhibition of histamine-stimulated adenylate cyclase in HGT-1 cells.
Similar content being viewed by others
References
Hug H, Sarre TF. Protein kinase C isoenzymes: divergence in signal transduction? Biochem J 1993;291:329–43.
Dekker LV, Parker PJ. Protein kinase C — a question of specificity. Trends in Biochem Sci 1994;218:73–7.
Hatt JF, Hanson PJ. Sites of action of protein kinase C on secretory activity in rat parietal cells. Am J Physiol 1989;256:G129-G138.
McKenna P, Williams JM, Gespach CP, Hanson PJ. Protein kinase C inhibits cyclic adenosine monophosphate generation by histamine and truncated glucagon-like peptide 1 in the human gastric cancer cell line HGT-1. Gut 1993;34:953–7.
Emly JF, Hanson PJ. Protein kinase C inhibits stimulation of adenylate cyclase by the histamineH 2 receptor in rat parietal cells. Agents Actions 1992;37:25–9.
Gespach C, Emami S, Chastre E. Membrane receptors in the gastrointestinal tract. BioSci Rep 8;199–232.
Laboisse CL, Augeron C, Couturier-Turpin M-H, Gespach C, Cheret A-M, Potet F. Characterization of a newly established human gastric cancer cell line HGT-1 bearing histamineH 2 receptors. Cancer Research 1982;42:1541–8.
Prost A, Emami S, Gespach C. Desensitization by histamine ofH 2 receptor-mediated adenylate cyclase activation in the human gastric cancer cell line HGT-1. FEBS Lett 1984;177:227–30.
Yasuda I, Kishimoto A, Tanaka S-I, Tominaga M, Sakurai A, Nishizuka Y. A synthetic peptide substrate for selective assay of protein kinase C. Biochem Biophys Res Commun 1990;166:1220–7.
Markwell MA, Haas SM, Bieber LL, Tolbert NE. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem 1978;87:206–10.
Makowske M, Ballester R, Cayre Y, Rosen OM. Immunochemical evidence that three protein kinase C isoenzymes increase in abundance during HL-60 differentiation induced by dimethyl sulphoxide and retinoic acid. J Biol Chem 1988;263:3402–10.
Davis PD, Hill CH, Keech E, Lawton G, Nixon JS, Sedgwick AD, Wadsworth J, Westmacott D, Wilkinson SE. Potent selective inhibitors of protein kinase C. FEBS Lett 1989;259:61–3.
Koide H, Ogita K, Kikkawa U, Nishizuka Y. Isolation and characterization of the∈ species of protein kinase C from rat brain. Proc Natl Acad Sci USA 1992;89:1149–53.
Chakravarthy BR, Bussey A, Whitfield JF, Sikorska M, Williams RE, Durkin JP. The direct measurement of protein kinase C (PKC) activity in isolated membranes using a selective peptide substrate. Anal Biochem 1991;196:144–50.
Houslay MD. ‘Crosstalk’: a pivotal role for protein kinase C in modulating relationships between signal transduction pathways. Eur J Biochem 1991;195:9–27.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McKenna, J.P., Williams, J.M. & Hanson, P.J. Theα isoform of protein kinase C inhibits histamine-stimulated adenylate cyclase activity in a particulate fraction of the human gastric cancer cell line HGT-1. Inflamm Res 44, 66–69 (1995). https://doi.org/10.1007/BF01793214
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01793214