Effects of phorbol ester and cholecystokinin on the intracellular distribution of protein kinase C in rabbit pancreatic acini.
Treatment of rabbit pancreatic acini with the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), resulted in a time- and dose-dependent decrease of soluble protein kinase C activity coinciding with an increase of protein kinase C activity in the particulate fraction. After 5 min, soluble protein kinase C activity had decreased to almost 10% of the corresponding control. Total extractable protein kinase C activity, however, remained unchanged, indicating that the decrease of soluble protein kinase C activity was not due to TPA-induced inactivation of the enzyme. The biologically inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate, did not induce such a translocation of protein kinase C. The half-maximal concentration for TPA-induced translocation of protein kinase C was 40 nM, and was equal to that for TPA-induced amylase secretion from isolated acini. This suggests that translocation of protein kinase C to the particulate fraction is an important step in TPA-induced activation of protein kinase C and enzyme secretion. On the other hand, cholecystokinin, a secretagogue of the calcium-mobilizing type, whose secretory action is thought to be mediated, at least in part, by protein kinase C, did not change the subcellular distribution of protein kinase C. In the presence of R59022 6-(2-[(4-fluorophenyl)phenylmethylene]-1-piperidinyl ) ethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, an inhibitor of diacylglycerol kinase activity, cholecystokinin produced a small but significant translocation of protein kinase C, suggesting that the inability of the hormone to induce translocation is not due to a rapid conversion of the diacylglycerol formed into phosphatidic acid.
Ederveen
A G
AG
Department of Biochemistry, University of Nijmegen, The Netherlands.
van Emst-de Vries
S E
SE
de Pont
J J
JJ
Willems
P H
PH
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002458:Cell Fractionation / Q000379:methods; D019852:Diacylglycerol Kinase; D007700:Kinetics; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000378:metabolism*; D011744:Pyrimidinones / Q000494:pharmacology; D011817:Rabbits; D012844:Sincalide / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology
D011744:Pyrimidinones; D013844:Thiazoles; C047505:R 59022; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D000681:Amylases; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate