7,12-Dimethylbenz[a]anthracene activates protein-tyrosine kinases Fyn and Lck in the HPB-ALL human T-cell line and increases tyrosine phosphorylation of phospholipase C-gamma 1, formation of inositol 1,4,5-trisphosphate, and mobilization of intracellular calcium.

Previous studies have shown that the immunosuppressive and carcinogenic polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA) impairs Ca(2+)-dependent transmembrane signaling in human and murine lymphocytes. The purpose of the present studies was to analyze potential mechanisms of immunosuppression by DMBA and to examine effects on Ca2+ homeostasis and antigen-receptor signaling in human T cells. DMBA produced a rapid and sustained increase in Ca2+ levels in HPB-ALL cells by release of cytoplasmic Ca2+.

Fc epsilon RI-mediated tyrosine phosphorylation and activation of the 72-kDa protein-tyrosine kinase, PTK72, in RBL-2H3 rat tumor mast cells.

In RBL-2H3 rat tumor mast cells, cross-linking the high-affinity IgE receptor Fc epsilon RI causes tyrosine phosphorylation of multiple proteins. These phosphoproteins include phospholipase C gamma 1, the beta and gamma subunits of the Fc epsilon RI, the Src family protein-tyrosine kinase Lyn, and a 72-kDa protein that coimmunoprecipitates from lysates of antigen-stimulated cells with antibody to the receptor beta subunit. We now present evidence that the 72-kDa Fc epsilon RI-associated protein is the protein-tyrosine kinase PTK72 that forms part of the antigen receptor complex in B lymphocytes.

Fc epsilon R1-mediated tyrosine phosphorylation of multiple proteins, including phospholipase C gamma 1 and the receptor beta gamma 2 complex, in RBL-2H3 rat basophilic leukemia cells.

In basophils, mast cells, and the RBL-2H3 tumor mast cell line, cross-linking the high-affinity immunoglobulin E receptor (Fc epsilon R1) stimulates a series of responses, particularly the activation of phospholipase C (PLC), that lead to allergic and other immediate hypersensitivity reactions. The mechanism of activation of PLC, however, is not clear. Here, we show that cross-linking Fc epsilon R1 on RBL-2H3 cells causes the tyrosine phosphorylation of at least 12 cellular proteins, including PLC gamma 1 (PLC gamma 1) and the receptor beta and gamma subunits.

Importance of bicarbonate ion for intracellular pH regulation in antigen- and ionomycin-stimulated RBL-2H3 mast cells.

In RBL-2H3 rat basophilic leukemia cells, Ca2+ influx and secretion are activated by antigens that crosslink IgE-receptor complexes and by the Ca2+ ionophore, ionomycin. Here we report that antigen-stimulated Ca2+ influx and secretion are impaired and ionomycin-induced responses are strongly inhibited following the removal of HCO3- from the medium. These results raised the possibility that HCO3(-)-dependent pH regulation mechanisms play a role in the cascade of events leading to mast cell activation.

Tyrosine kinase-dependent phosphatidylinostiol turnover and functional responses in the Fc epsilon R1 signalling pathway.

In RBL-2H3 rat basophilic leukemia cells, Fc epsilon R1 crosslinking by multivalent antigen stimulates phosphatidylinositol (PI) turnover and Ca2+ influx and causes functional responses that include secretion, membrane ruffling and actin polymerization. Here, we show that the tyrosine kinase inhibitor, genistein, inhibits antigen-induced PI turnover, determined from assays of 1,4,5-inositol trisphosphate production, and impairs receptor-mediated secretion, ruffling and actin polymerization. Genistein has little effect on several functional responses to stimuli that bypass PI hydrolysis (ionomycin-induced secretion, phorbol ester-induced ruffling) but it inhibits phorbol ester-induced actin polymerization.