The alpha isoform of protein kinase C inhibits histamine-stimulated adenylate cyclase activity in a particulate fraction of the human gastric cancer cell line HGT-1.
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. The alpha and epsilon isoforms of protein kinase C were detected in HGT-1 cells and in a 40,000 x 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 concentration-dependent manner by anti-peptide antibody to protein kinase C alpha, but not to protein kinase C epsilon. Addition of Ca2+ and TPA to the 40,000 x g particulate fraction stimulated the phosphorylation of the protein kinase C substrate myelin basic peptide 4-14. Protein kinase C alpha is probably the isoform responsible for inhibition of histamine-stimulated adenylate cyclase in HGT-1 cells.
McKenna
J P
JP
Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
Williams
J M
JM
Hanson
P J
PJ
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D002118:Calcium / Q000494:pharmacology; D002458:Cell Fractionation; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000067956:Adenylyl Cyclase Inhibitors; D007527:Isoenzymes; D004676:Myelin Basic Protein; D006632:Histamine; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium