Staurosporine stimulates expression of the urokinase-type (u-PA) plasminogen activator in LLC-PK1 cells.
In LLC-PK1 porcine epithelial cells, the urokinase-type plasminogen activator (u-PA) mRNA and protein can be induced either by stimulation of the protein kinase C (PKC) pathway using a tumor promoter (PMA) or by stimulation of the protein kinase A (PKA) pathway with calcitonin (SCT). By contrast, addition of 10(-7) M staurosporine, an inhibitor of PKC, to LLC-PK1 cells also stimulated urokinase production. In contrast to the in vitro situation (where staurosporine inhibited PKC activity), in the cell-culture system the microbial agent caused an early translocation of PKC and inhibited PKA. Addition of staurosporine together with PMA or with SCT further increased urokinase mRNA and protein synthesis. Maximal stimulation was obtained when all 3 agents were added together. We thus assume that in LLC-PK1 cells the PKA and PKC signal-transferring pathways can function independently.
Dierks-Ventling
C
C
Friedrich Miescher Institute, Basel, Switzerland.
Knesel
J
J
Nagamine
Y
Y
Hemmings
B A
BA
Pehling
G
G
Fischer
F
F
Fabbro
D
D
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology; D002451:Cell Compartmentation / Q000187:drug effects; D002478:Cells, Cultured; D004848:Epithelium / Q000201:enzymology; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D011493:Protein Kinase C / Q000502:physiology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D019311:Staurosporine; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D000470:Alkaloids; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D002116:Calcitonin; D011494:Protein Kinases; D011493:Protein Kinase C; D014568:Urokinase-Type Plasminogen Activator; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate