Abstract
The specific phosphatase inhibitor, okadaic acid, increases the level of mRNA for the receptor for urokinase-type plasminogen activator (u-PAR) in 8 out of 13 human cell lines. The strongest increase (90-fold) was observed in A549 lung carcinoma cells, in which it was partly traced back to an increased transcription of the u-PAR gene. There was a parallel but less pronounced increase in the u-PAR protein level. These findings indicate that u-PAR gene transcription is regulated by one or more factors that are constitutively phosphorylated and are dephosphorylated by okadaic acid-sensitive phosphatases. A lack of additivity of u-PAR induction by okadaic acid and by the protein kinase C activator, PMA, in the A549 cells suggests that the regulatory factors affected by okadaic acid are phosphorylated by protein kinase C.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Northern
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Cell Line
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Ethers, Cyclic / pharmacology*
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Gene Expression Regulation
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Humans
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Okadaic Acid
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Organ Specificity / genetics
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Phosphoprotein Phosphatases / antagonists & inhibitors*
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Plasminogen Activators / genetics*
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Plasminogen Activators / metabolism
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RNA, Messenger / metabolism
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Receptors, Cell Surface / genetics*
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Receptors, Cell Surface / metabolism
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Receptors, Urokinase Plasminogen Activator
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription, Genetic / drug effects*
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Transforming Growth Factor beta / pharmacology
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Tumor Cells, Cultured
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Urokinase-Type Plasminogen Activator / metabolism*
Substances
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Ethers, Cyclic
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PLAUR protein, human
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Urokinase Plasminogen Activator
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Transforming Growth Factor beta
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Okadaic Acid
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Phosphoprotein Phosphatases
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Plasminogen Activators
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Urokinase-Type Plasminogen Activator
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Tetradecanoylphorbol Acetate