N-acetyl-L-cysteine inhibits antigen-mediated Syk, but not Lyn tyrosine kinase activation in mast cells.
High affinity IgE receptors (alpha beta gamma 2) mediate the activation of the non-receptor tyrosine kinases Lyn and Syk. Here we show that the antioxidant drug N-acetyl-L-cysteine (NAC) inhibits antigen-mediated Syk activation whereas Lyn activation and phosphorylation of beta and gamma is maintained. Furthermore, NAC inhibits antigen-mediated calcium mobilization and exocytosis in a dose-dependent manner, but does not inhibit ionomycin-induced exocytosis. These data support a model in which the activation of Lyn is responsible for receptor phosphorylation and precedes the activation of Syk. The inhibition of Syk activation by NAC may be relevant to B and T cell antigen receptors, which are also linked to Syk/ZAP70 tyrosine kinases.
Vallé
A
A
Molecular Allergy and Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
Kinet
J P
JP
D000111:Acetylcysteine / Q000494:pharmacology*; D000941:Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors*; D005089:Exocytosis / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D000072377:Syk Kinase; D019061:src-Family Kinases
D000941:Antigens; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002118:Calcium; D000111:Acetylcysteine