SYK IS ACTIVATED BY PHOSPHOTYROSINE-CONTAINING PEPTIDES REPRESENTING THE TYROSINE-BASED ACTIVATION MOTIFS OF THE HIGH-AFFINITY RECEPTOR FORIGE

Engagement of the high affinity receptor for immuno globulin E (Fc eps ilon RI) on the surface of mast cells induces tyrosine phosphorylation of numerous cellular proteins, Syk, one of several non-receptor prote in tyrosine kinases implicated in Fc epsilon RI signaling, is activate d following receptor cross-linking and associates with phosphorylated gamma subunits of Fc epsilon RI. We previously showed that the Src hom ology 2 (SH2) domains of Syk bind with high affinity to the conserved tyrosine-based activation motif (TAM) of the gamma subunit in vitro, I n this report, we show that a tyrosine-phosphorylated gamma TAM peptid e induced tyrosine phosphorylation of Syk in RBL-2H3 cell lysates and stimulated Syk kinase activity 10-fold in vitro, with half-maximal act ivation at 1-2 mu M. A similar beta subunit TAM peptide showed much lo wer stimulation of Syk tyrosine phosphorylation and kinase activity. P hosphopeptide-induced activation was inhibited by an antiserum to the carboxyl-terminal tail of Syk, suggesting that those amino acids are a lso involved in Syk activation, These results indicate that the cataly tic domain of Syk may be regulated by intramolecular interactions with adjacent domains and suggest that Syk binding to phosphorylated gamma subunits following Fc epsilon RI engagement in vivo stimulates Syk ki nase activity.