Inorganic mercury inhibits the activation of LAT in T-cell receptor-mediated signal transduction.
Little is known as to the molecular mechanisms involved with mercury intoxication at very low levels. Although the mechanism is not known, animal studies have nevertheless shown that low levels of mercury may target the immune system. Inorganic mercury (Hg2+) at very low (but non-toxic) levels can disrupt immune system homeostasis, in that genetically susceptible rodents develop idiosyncratic autoimmune disease, which is associated with defective T-cell function. T lymphocyte function is intimately coupled to the T-cell receptor. We have previously reported that on a molecular level, low concentrations of Hg2+ disrupt signaling from the T-cell receptor by interfering with activation of Ras and ERK MAP kinase. In this report we expand upon those results by showing that in T lymphocytes exposed to low concentration of Hg2+, Ras fails to become properly activated because upstream of Ras in the T cell signal transduction pathway, the important scaffolding element Linker for Activation of T Cells (LAT) fails to become properly phosphorylated. Hypo-phosphorylation of LAT occurs, because upstream of LAT, the LAT reactive tyrosine kinase ZAP-70 is also not properly activated in Hg2+ treated cells.
Ziemba
Stamatina E
SE
Department of Immunology & Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Mattingly
Raymond R
RR
McCabe
Michael J
MJ
Rosenspire
Allen J
AJ
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000096:biosynthesis*; D008627:Mercuric Chloride / Q000494:pharmacology*; D010750:Phosphoproteins / Q000096:biosynthesis*; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000890:Anti-Infective Agents; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D008627:Mercuric Chloride; D051746:ZAP-70 Protein-Tyrosine Kinase; D018631:ras Proteins