Changes in protein phosphorylation in wild-type and nickel-resistant cells and their involvement in morphological elongation.
Treatment of wild-type Balb/c-3T3 cells with NiCl2 or N6,2-O-dibutyl-adenosine 3',5'-monophosphate (Bt2-cAMP) resulted in a high degree and frequency of cellular elongation. Nickel-resistant Balb/c-3T3 cells (B200) treated with Bt2-cAMP elongated at the same exposure concentration as wild-type cells. In contrast, treatment of the nickel-resistant cells with both non-cytotoxic and cytotoxic doses of NiCl2 failed to induce elongation. Nickel-resistant cells had two-thirds of the total protein-phosphorylation activity of wild-type cells. Both cAMP and NiCl2 enhanced phosphorylation of specific proteins in intact wild-type cells as detected by 32p autoradiography of these proteins separated on two-dimensional gels. A nickel-dependent phosphorylation of specific proteins is seen following NiCl2 treatment of wild-type cells but was not observed in B200 cells. In contrast, the pattern of Bt2-cAMP-stimulated protein phosphorylation was quite similar in both wild-type and nickel-resistant cells. Although it is unclear at present how nickel ions affect the cellular protein-phosphorylation system, these results suggested that targets controlling cellular elongation are sensitive to nickel, are altered in nickel-resistant cells and appear to involve protein phosphorylation. Further characterization of these targets may help in understanding the mechanisms of nickel carcinogenesis.
Wang
X W
XW
Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Costa
M
M
D016475:3T3 Cells; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004351:Drug Resistance; D015180:Electrophoresis, Gel, Two-Dimensional; D007700:Kinetics; D051379:Mice; D009024:Morphogenesis; D009532:Nickel / Q000494:pharmacology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
D011506:Proteins; D003994:Bucladesine; D009532:Nickel; D000242:Cyclic AMP; D011494:Protein Kinases