Comparison of the effect of tautomycin and phorbol ester on protein kinase C in a cell-free system.
The effect of tautomycin (TM) on protein kinase C (PKC) was studied in a cell-free system. TM, like phorbol dibutyrate (PDBu), enhanced both base-line and Ca2+/phospholipids-dependent protein kinase activity. However, PDBu but not TM increased the affinity of the enzyme for calcium ions (Ca2+), suggesting that TM is a new activator of PKC, distinct from PDBu. In the presence of 10 micrograms/ml phosphatidyl inositol, the activity of PKC reached maximum at 10(-3) M Ca2+ concentration when the other co-factors were absent. Both TM and PDBu increased the maximum level of PKC activity at the optimum concentration of Ca2+, suggesting that they interacted with the site of PKC which is distinct from the site where Ca2+ interacts. TM and PDBu did not activate the enzyme when protamine sulfate in place of histone III-S was used as a substrate, indicating that they activate PKC by affecting the regulatory domain of the enzyme.
Magae
J
J
Department of Agricultural Chemistry, University of Tokyo, Japan.
Osada
H
H
Nagai
K
K
Yamasaki
M
M
Isono
K
K
D000935:Antifungal Agents / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002474:Cell-Free System; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011714:Pyrans; D013141:Spiro Compounds; D014407:Tumor Cells, Cultured / Q000201:enzymology
D000935:Antifungal Agents; D010716:Phosphatidylinositols; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D002118:Calcium