Staurosporine can inhibit the G1-S transition induced by a calcium channel agonist by blocking the pathway independent of phorbol ester-sensitive protein kinase C in rat thyroid cells (FRTL-5).
IGF-I, when added to TSH-primed FRTL-5 cells, can induce a long lasting Ca2+ influx followed by the DNA synthesis. BAY K8644, a Ca2+ channel agonist, can also induce the DNA synthesis in TSH-treated cells. Staurosporine, which is known to be a potent inhibitor of protein kinase C(PKC) strongly inhibited the DNA synthesis caused by these two reagents. However, in PKC-down regulated cells, IGF-I and BAY K8644 could also evoke the DNA synthesis and the inhibitory effect of staurosporine persisted. These inhibitory effects did not relay on inhibition of the Ca2+ influx induced by BAY K8644. Thus these results demonstrate that staurosporine acts at a point distal to Ca2+ influx to inhibit G1-S transition and this staurosporine-sensitive pathway possibly mediates the mitogenic signal in PKC-independent manner.
Takano
T
T
Department of Laboratory Medicine, Osaka University Medical School, Japan.
Takada
K
K
Tada
H
H
Nishiyama
S
S
Amino
N
N
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D002460:Cell Line; D016193:G1 Phase / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D016196:S Phase / Q000187:drug effects*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology* / Q000201:enzymology
D000470:Alkaloids; D015220:Calcium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium