Mercuric chloride mediates a protein sulfhydryl modification-based pathway of signal transduction for activating Src kinase which is independent of the phosphorylation/dephosphorylation of a carboxyl terminal tyrosine.
Little is known about the regulatory mechanism of c-Src kinase in cells except the suggested regulation through phosphorylation and dephosphorylation of its carboxyl terminal tyrosine residue (Y527). We here demonstrated that exposure of NIH3T3 cells to mercuric chloride (HgCl2) induces both aggregation and activation of Src kinase protein through a redox-linked mechanism. The aggregation of Src proteins was suggested to be induced by the sulfhydryl groups-to-Hg2+ reaction-mediated polymerization of cell membrane proteins to which the Src proteins associate noncovalently. The possibility was ruled out that the aggregation occurred secondarily to the promotion of protein tyrosine phosphorylation. Further study revealed that the Src kinase was activated by HgCl2 at least in part independent of the known Csk kinase-linked or Y527-phosphorylation/dephosphorylation-mediated control. Correspondingly, CNBr cleavage mapping of phosphopeptides for autophosphorylated c-Src protein demonstrated selective promotion of phosphorylation at Y416 in HgCl2-treated cells without obvious change in the phosphorylation level at Y527. These results suggest a unique protein sulfhydryl modification-based pathway of signal transduction for activating Src kinase in NIH3T3 cells.
Department of Immunology, Nagoya University School of Medicine, Japan.
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Akhand
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Kato
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Koike
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Hamaguchi
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Suzuki
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Nakashima
D016475:3T3 Cells; D000818:Animals; D003488:Cyanogen Bromide; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D008627:Mercuric Chloride / Q000494:pharmacology*; D051379:Mice; D016296:Mutagenesis; D010449:Peptide Mapping; D010766:Phosphorylation; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D014443:Tyrosine; D008627:Mercuric Chloride; D019061:src-Family Kinases; D003488:Cyanogen Bromide