Redox-linked ligand-independent cell surface triggering for extensive protein tyrosine phosphorylation.
Exposure of lymphocytes to 0.2-2 mM HgCl2, a thiol-reactive heavy metal, induced extensive tyrosine phosphorylation of multiple cellular proteins. The phosphorylation started as quickly as 5 s after exposure to HgCl2, and was irreversible. Another 3 thiol-reactive chemicals also displayed similar, though less marked, actions, whereas dithiothreitol, a reducing agent, antagonized the HgCl2 action. The demonstrated new action of HgCl2 indispensably required membrane-intact cells as a target. Whereas exposure of lymphocytes to > 0.2 mM HgCl2 caused rapid cell death, 0.01-0.1 mM HgCl2 affected the cells so as to accelerate their c-fos transcription. These results suggest a novel redox-linked mechanism of cell surface triggering of intracellular protein kinase activity, which is independent of receptor-ligand interactions.
Rahman
S M
SM
Department of Immunology, Nagoya University School of Medicine, Japan.
Pu
M Y
MY
Hamaguchi
M
M
Iwamoto
T
T
Isobe
K
K
Nakashima
I
I
D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D006046:Gold / Q000494:pharmacology; D017612:Gold Compounds; D008024:Ligands; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008627:Mercuric Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D017612:Gold Compounds; D008024:Ligands; D011506:Proteins; C038016:gold chloride; D014443:Tyrosine; D008627:Mercuric Chloride; D002731:4-Chloromercuribenzenesulfonate; D006046:Gold