Epidermal growth factor and 12-tetradecanoyl phorbol 13-acetate induction of urokinase in A431 cells.
The signal transduction pathways of urokinase (u-PA) in A431 cells, a human epidermoid carcinoma cell line, were studied using the inducers EGF and TPA. Based on the following observations, we conclude that the two pathways are different: (1) The effects are additive; (2) EGF induction of u-PA was not compromised either by down-regulation of PKC or selective inhibition of the same by H7; (3) 8-Br-cAMP has no effect by itself; however, it inhibits the EGF effect and doubles the TPA induction of u-PA; (4) after EGF-induced tyrosine phosphorylations are completed, addition of TPA can still induce u-PA, an effect that can be blocked by the addition of the tyrosine phosphorylation inhibitor, genistein, indicating that the two agents induce different tyrosine phosphorylation; (5) in 2-dimensional electrophoresis of 32P-labeled cell lysates, inducer-specific differences in the intensity of spots can be observed. Some of the spots weakened by genistein (tyrosine phosphorylations) are different, depending on the inducer used.
Kessler
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Department of Experimental Biology, Roswell Park Cancer Institute, New York State Department of Health, Buffalo 14263.
Markus
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D002863:Chromogenic Compounds / Q000032:analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D004790:Enzyme Induction / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D002863:Chromogenic Compounds; D009842:Oligopeptides; D014443:Tyrosine; D004815:Epidermal Growth Factor; C060237:H-norleucyl-hexahydrotyrosyl-lysine-4-nitroanilide; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate