Phosphorylation/Dephosphorylation steps are crucial for the induction of CYP2B1 and CYP2B2 gene expression by phenobarbital

Biochem Biophys Res Commun. 1999 Oct 22;264(2):530-6. doi: 10.1006/bbrc.1999.1544.


The effects of several protein kinase activators and protein phosphatase inhibitors on the phenobarbital (PB)-induced gene expression of CYP2B1 and CYP2B2 (CYP2B1/2B2) in adult rat hepatocytes were investigated. Insulin, epidermal growth factor, interleukin 6, cAMP, phorbol 12-myristate 13-acetate, tumor necrosis factor alpha, vanadate, and okadaic acid were found to suppress the induction of CYP2B1/2B2 at mRNA and protein levels in hepatocytes. cAMP and vanadate completely suppressed the induction of CYP2B1/2B2 gene expression in both rat hepatocytes and liver. The addition of genistein to vanadate-treated hepatocytes partially recovered the induction of CYP2B1/2B1 gene expression by PB. These results of the present study demonstrate that phosphorylation/dephosphorylation steps are crucial for the induction of CYP2B1/2B2 gene expression by PB.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Cells, Cultured
  • Cytochrome P-450 CYP2B1 / biosynthesis*
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Enzyme Activation / drug effects
  • Enzyme Induction / drug effects
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Genistein / pharmacology
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Phenobarbital / antagonists & inhibitors
  • Phenobarbital / pharmacology*
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Steroid Hydroxylases / biosynthesis*
  • Vanadates / pharmacology


  • Enzyme Inhibitors
  • Vanadates
  • Cytochrome P-450 Enzyme System
  • Genistein
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2B1
  • steroid 16-beta-hydroxylase
  • Protein Kinase C
  • Phosphoprotein Phosphatases
  • Phenobarbital