Mercury Alters B‑Cell Protein Phosphorylation
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Abstract
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 Hg<sup>2+</sup>. These changes were compared
to changes in the phosphoproteome that were induced by pervanadate
or okadaic acid exposure. Both 250 μM HgCl<sub>2</sub> and pervanadate,
a known phosphotyrosine phosphatase inhibitor, caused an increase
in the number of proteins identified after TiO<sub>2</sub> affinity
selection and LC-MS/MS analysis. Pervanadate treatment had a larger
effect than Hg<sup>2+</sup> on the number of Scansite motifs that
were tyrosine-phosphorylated, 17, and Ingenuity canonical signaling
pathways activated, 4, with score >5.0. However, Hg<sup>2+</sup> 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
Hg<sup>2+</sup> overlap with those of pervanadate, indicates that
at high concentrations Hg<sup>2+</sup> inhibits protein tyrosine phosphatases