Acute 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure results in enhanced tyrosylphosphorylation and expression of murine hepatic cyclin dependent kinases

Biochem Biophys Res Commun. 1993 Dec 30;197(3):1070-7. doi: 10.1006/bbrc.1993.2587.

Abstract

An increase in tyrosine phosphorylation of two hepatic S9 proteins migrating at 34 and 33 kDa that cross-reacted with anti-PSTAIR antibody on immunoblots was seen 24 h after administration of a single dose of 0.25, 0.5, 1 or 2 micrograms 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg to C57BL/6J female mice. Two hepatic S9 proteins migrating at 34 and 33 kDa that cross-reacted with anti-cdc2 C-terminus antibody on immunoblots were observed in corn oil control mice; increased expression of these proteins was seen with increasing doses of TCDD. A maximal increase in expression of 3-times the control was observed at 1 and 2 micrograms TCDD/kg for both p34 and p33. The stimulation of enhanced tyrosylphosphorylation and expression of cyclin dependent kinases p34cdc2 and p3cdk2 by TCDD is consistent with a mechanism of action of TCDD toxicity associated with stimulation of cellular proliferation.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • CDC2 Protein Kinase / biosynthesis*
  • CDC2-CDC28 Kinases*
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases*
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Gene Expression / drug effects
  • Immunoblotting
  • Liver / drug effects
  • Liver / enzymology*
  • Mice
  • Mice, Inbred C57BL
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism
  • Phosphotyrosine
  • Polychlorinated Dibenzodioxins / toxicity*
  • Protein Kinases / biosynthesis*
  • Protein Serine-Threonine Kinases*
  • Reference Values
  • Tyrosine / analogs & derivatives*
  • Tyrosine / analysis
  • Tyrosine / metabolism

Substances

  • Antibodies, Monoclonal
  • Phosphoproteins
  • Polychlorinated Dibenzodioxins
  • Phosphotyrosine
  • Tyrosine
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • CDC2-CDC28 Kinases
  • Cdk2 protein, mouse
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases