Synergistic modulation of ectoCa2(+)-ATPase activity of hepatoma (Li-7A) cells by epidermal growth factor and cyclic AMP.
A mercurial-insensitive ectoATPase, which was more active with CaATP than with MgATP, was induced when human hepatoma (Li-7A) cells were cultured in the presence of epidermal growth factor (EGF) and cholera toxin. Cholera toxin could be replaced by forskolin, 8-Br-cAMP, butyryl-cAMP, and dibutyryl-cAMP. Requirement for EGF was specific, but EGF was ineffective if added more than 24 h after the addition of forskolin or cholera toxin. It was concluded that induction of the ectoCa2(+)-ATPase was a consequence of the synergistic actions of EGF and cyclic AMP. The tyrosine kinase activity of the EGF receptor was essential for the induction of ectoCa2(+)-ATPase, since enzyme induction was abolished by a tyrosine kinase inhibitor, genistein. Cycloheximide and actinomycin D were also inhibitory to enzyme induction, indicating that enhancement of enzyme activity by EGF and cAMP was not due to post-translational modification. The results of this and previous investigations established that the two ectoATPases of Li-7A cells are under different regulation.
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Department of Biology, Northeastern University, Boston, Massachusetts 02115.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D008113:Liver Neoplasms; D013997:Time Factors
D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004815:Epidermal Growth Factor; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D000252:Calcium-Transporting ATPases; D006854:Hydrocortisone; D004121:Dimethyl Sulfoxide