Mercury Alters B‑Cell Protein Phosphorylation Profiles

• Published in: Journal of proteome research Vol. 13; no. 2; pp. 496 - 505
• Main Authors: Caruthers, Nicholas J, Stemmer, Paul M, Shin, Namhee, Dombkowski, Alan, Caruso, Joseph A, Gill, Randal, Rosenspire, Allen
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07-02-2014
• Subjects: B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Blood Proteins - metabolism; Cell Line; Chromatography, Affinity; Humans; Mercury - pharmacology; Phosphorylation; Tandem Mass Spectrometry; toxicology; phosphoproteomics; phosphotyrosine; B cell; Hg2; phosphoprotein; mercury; WEHI-231; mass spectrometry; TiO2
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/pr400657k

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.