SYK PROTEIN-TYROSINE KINASE IS REGULATED BY TYROSINE-PHOSPHORYLATED IG-ALPHA IG-BETA IMMUNORECEPTOR TYROSINE ACTIVATION MOTIF BINDING AND AUTOPHOSPHORYLATION

Syk is a cytoplasmic protein-tyrosine kinase containing two amino-term inal Src homology 2 domains that is activated following ligation of th e B cell antigen receptor. Syk activation in B cells correlates with S yk tyrosine phosphorylation as well, as with Syk SH2-mediated associat ion with the tyrosine-phosphorylated Ig alpha and Ig beta B cell antig en receptor subunits. Tyrosine-phosphorylated peptide 20-mers represen ting Ig alpha and Ig beta immunoreceptor tyrosine activation motifs we re synthesized and found to stimulate the specific activity of Syk by as much as 10-fold in vitro. Maximal phosphopeptide-induced Syk activa tion required both Syk SH2 domains and phosphorylation of both tyrosin e residues present in the immunoreceptor tyrosine activation motif, Th e biochemical mechanism responsible for the phosphopeptide-induced Syk enzyme activation appears to be a function of Syk autophosphorylation . Our observations suggest the association of Syk tandem SH2 domains w ith the tyrosine-phosphorylated Ig alpha and/or Ig beta immunoreceptor tyrosine activation motifs in B cells stimulates Syk autophosphorylat ion leading to Syk enzyme activation.