Prolonged activation of protein kinase C induces transcription and expression of the alpha 1B adrenergic receptor gene in DDT1 MF-2 cells.
Protein kinase C (PKC) regulates many cellular functions; we have examined the role of PKC in the regulation of the alpha 1B adrenergic receptor gene. Exposure of DDT1 MF-2 cells to phorbol 12-myristate 13-acetate (PMA) (10 nM) increased values of alpha 1B receptor mRNA with peak changes found at 4 h (3.2-fold increase). Increased values of alpha 1B receptor mRNA occurred at PMA concentrations as low as 10 pM with a maximal response at 100 nM. Also, PMA induced a time-dependent increase in the number of alpha 1B receptors. Stimulation of cells with phenylephrine led to an increase in IP3 production after 3, 6, and 12 h of treatment with PMA. Induction of the alpha 1B receptor mRNA was suppressed by the PKC inhibitors H7 (1-(5-isoquinolinylsulsulfonyl)2-methylpiperazine) and saurosporine; the inactive phorbol ester 4 alpha-phorbol didecanoate and calcium ionophores A23187 and Bay K8644 did not increase alpha 1B receptor mRNA. The half-life of the alpha 1B receptor mRNA was unchanged by PMA. Nuclear runoff assays demonstrated that PMA produced a marked increase in the transcription rate of alpha 1B adrenergic receptor expression is mediated by a PKC-dependent mechanism that occurs at the level of transcription.
Department of Medicine, Stanford University School of Medicine, California.
Z W
ZW
Hu
X Y
XY
Shi
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M
Sakaue
B B
BB
Hoffman
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D008647:Mesocricetus; D010656:Phenylephrine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000235:genetics* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate