Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Igα/Igβ immunoreceptor tyrosine activation motif binding and autophosphorylation

Abstract

Syk is a cytoplasmic protein-tyrosine kinase containing two amino- terminal Src homology 2 domains that is activated following ligation of the B cell antigen receptor. Syk activation in B cells correlates with Syk tyrosine phosphorylation as well as with Syk SH2-mediated association with the tyrosine-phosphorylated Igα and Igβ B cell antigen receptor subunits. Tyrosine-phosphorylated peptide 20-mers representing Igα and Igβ immunoreceptor tyrosine activation motifs were synthesized and found to stimulate the specific activity of Syk by as much as 10-fold in vitro. Maximal phosphopeptide-induced Syk activation required both Syk SH2 domains and phosphorylation of both tyrosine residues present in the immunoreceptor tyrosine activation motif. The 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 with the tyrosine-phosphorylated Igα and/or Igβ immunoreceptor tyrosine activation motifs in B cells stimulates Syk autophosphorylation leading to Syk enzyme activation.