Phenylarsine oxide (PAO) blocks antigen receptor-induced calcium response and tyrosine phosphorylation of a distinct group of proteins.
Antigen receptor (AgR) crosslinking by antigens or AgR-specific antibodies induces a cascade of enzymatic events in lymphocytes which involves activation of several non-receptor tyrosine- and serine/threonine kinases, phosphatases, phospholipases, etc. Here we show data demonstrating that a thiol group-reactive protein tyrosine phosphatase (PTP) inhibitor, phenylarsine oxide (PAO), uncouples a crucial part of the signaling events induced by anti-IgM or anti-Leu-4 (CD3) in human tonsil B lymphocytes, BL41 and Daudi B cell lines and Jurkat T lymphoma cells. PAO treatment (10 microM) resulting in distinct modification of AgR-induced tyrosine phosphorylation pattern inhibited the AgR-mediated calcium response (Ca++ release and influx) of all of these cells completely. Since this treatment did not alter the cell viability and the binding capacity of the AgR crosslinking antibodies, alteration of the tyrosine phosphorylation pattern and blockage of the calcium response indicate prompt inactivation of essential signal transduction element(s).
Rozsnyay
Z
Z
Laboratory of Immunoregulation, Vienna International Research Cooperation Center at SFI, Austria.
Sarmay
G
G
Gergely
J
J
D001152:Arsenicals / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011946:Receptors, Antigen / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D001152:Arsenicals; D017252:CD3 Complex; D007075:Immunoglobulin M; D011946:Receptors, Antigen; C029341:oxophenylarsine; D014443:Tyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D002118:Calcium