Acute 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure results in enhanced tyrosylphosphorylation and expression of murine hepatic cyclin dependent kinases.
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.
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Section of Cellular Physiology, Paracelsian, Inc., 222 Langmuir Laboratories, Cornell Technology Park, Ithaca, NY 14850.
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D000818:Animals; D000911:Antibodies, Monoclonal; D016203:CDC2 Protein Kinase / Q000096:biosynthesis*; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D019000:Phosphotyrosine; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011494:Protein Kinases / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases; D012016:Reference Values; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
D000911:Antibodies, Monoclonal; D010750:Phosphoproteins; D000072317:Polychlorinated Dibenzodioxins; D019000:Phosphotyrosine; D014443:Tyrosine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases