Okadaic acid strongly increases gene transcription, mRNA and protein level for the urokinase receptor in human A549 cells.
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.
Lund
L R
LR
Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
Danø
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D015152:Blotting, Northern; D002460:Cell Line; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D019319:Okadaic Acid; D009928:Organ Specificity / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010960:Plasminogen Activators / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D004988:Ethers, Cyclic; C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016212:Transforming Growth Factor beta; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate