Mercury Alters B‑Cell Protein Phosphorylation Profiles

Environmental exposure to mercury is suggested to contribute to
human immune dysfunction. To shed light on the mechanism, we identified
changes in the phosphoproteomic profile of the WEHI-231 B cell line
after intoxication with Hg2+. These changes were compared
to changes in the phosphoproteome that were induced by pervanadate
or okadaic acid exposure. Both 250 μM HgCl2 and pervanadate,
a known phosphotyrosine phosphatase inhibitor, caused an increase
in the number of proteins identified after TiO2 affinity
selection and LC-MS/MS analysis. Pervanadate treatment had a larger
effect than Hg2+ on the number of Scansite motifs that
were tyrosine-phosphorylated, 17, and Ingenuity canonical signaling
pathways activated, 4, with score >5.0. However, Hg2+ had
a more focused effect, primarily causing tyrosine-phosphorylation
in src homology 2 domains in proteins that are in the B cell receptor
signaling pathway. The finding that many of the changes induced by
Hg2+ overlap with those of pervanadate, indicates that
at high concentrations Hg2+ inhibits protein tyrosine phosphatases.