CRITICAL ROLE FOR THE TYROSINE KINASE SYK IN SIGNALING THROUGH THE HIGH-AFFINITY IGE RECEPTOR OF MAST-CELLS

Activation of the high affinity IgE receptor (Fc epsilon RI) of mast c ells, a member of the antigen receptor family, leads to the release of allergic mediators, a critical event in the onset of immediate hypers ensitivity. Stimulation of Fc epsilon RI results in the rapid associat ion and activation of the Syk tyrosine kinase. Using Syk-deficient mas t cells we show that they fail to degranulate, synthesize leukotrienes and secrete cytokines when stimulated through Fc epsilon RI, conclusi vely demonstrating an essential role for Syk in Fc epsilon Phi RI sign alling, Furthermore, our data strongly supports a model of Fc epsilon RI engagement leading to the sequential activation of the tyrosine kin ases Lyn and then Syk, A similar mechanism is likely to apply to signa l transduction through all members of the antigen receptor family.