Tyrosine phosphorylation coupled to IgE receptor-mediated signal transduction and histamine release.
Antigen-induced cross-linking of IgE bound to its receptors at the surface of basophils or mast cells initiates a number of biochemical events culminating in the release of histamine-containing granules. In the present study, we investigated the possible involvement of tyrosine phosphorylation in signaling by the high-affinity IgE receptor (Fc epsilon RI). Cross-linking of Fc epsilon RI in rat basophilic leukemia cells (RBL-2H3) led to the phosphorylation of several proteins on tyrosine, the most prominent having a mass of 72 kDa. Tyrosine phosphorylation was rapid, detectable 1 min after stimulation, and correlated with both the time course and antigen dose for histamine release. Reversal of Fc epsilon RI cross-linking prevented continuation of the degranulation process and resulted in rapid loss of tyrosine phosphorylation. The receptor-mediated tyrosine phosphorylation was still induced in the absence of calcium in the medium. Depletion of protein kinase C with phorbol 12-myristate 13-acetate did not dramatically affect the tyrosine phosphorylation signal or the release of histamine. In contrast, the calcium ionophore A23187 induced histamine release in the absence of a perceptible increase in protein tyrosine phosphorylation. Thus, tyrosine phosphorylation is an early signal following Fc epsilon RI aggregation, independent of the exocytotic process itself. Taken together, our findings functionally link protein phosphorylation on tyrosine residues to Fc epsilon RI-mediated signal transduction leading to histamine release.
Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
M
M
Benhamou
J S
JS
Gutkind
K C
KC
Robbins
R P
RP
Siraganian
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002122:Calcium Chloride / Q000494:pharmacology; D002460:Cell Line; D006636:Histamine Release / Q000187:drug effects; D007073:Immunoglobulin E / Q000276:immunology*; D007700:Kinetics; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014443:Tyrosine
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D010750:Phosphoproteins; D011961:Receptors, Fc; D017455:Receptors, IgE; D007073:Immunoglobulin E; D000001:Calcimycin; D014443:Tyrosine; D011493:Protein Kinase C; D002122:Calcium Chloride; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium