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 Hg(2+). 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 Hg(2+) on the number of Scansite motifs that were tyrosine-phosphorylated, 17, and Ingenuity canonical signaling pathways activated, 4, with score >5.0. However, Hg(2+) 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(2+) overlap with those of pervanadate, indicates that at high concentrations Hg(2+) inhibits protein tyrosine phosphatases.
Institute of Environmental Health Sciences, ‡Department of Pediatrics, and §Department of Immunology and Microbiology, Wayne State University , Detroit, Michigan 48201, United States.
Nicholas J
NJ
Caruthers
Paul M
PM
Stemmer
Namhee
N
Shin
Alan
A
Dombkowski
Joseph A
JA
Caruso
Randal
R
Gill
Allen
A
Rosenspire
D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D002460:Cell Line; D002846:Chromatography, Affinity; D006801:Humans; D008628:Mercury / Q000494:pharmacology*; D010766:Phosphorylation; D053719:Tandem Mass Spectrometry
D001798:Blood Proteins; D008628:Mercury