SYK ACTIVATION AND DISSOCIATION FROM THE B-CELL ANTIGEN RECEPTOR IS MEDIATED BY PHOSPHORYLATION OF TYROSINE-130

Syk (p72(syk)) is a 72-kDa cytoplasmic protein-tyrosine kinase that se rves as an essential component of the signal transduction machinery co upled to the B-cell antigen receptor. Syk is recruited to the receptor when it is cross-linked and, in response, becomes tyrosine-phosphoryl ated and activated before it dissociates from the receptor and appears in the cytoplasm. To begin to explore how tyrosine phosphorylation af fects Syk activation and receptor binding, Tyr-130, which is localized within the Syk inter-Src homology 2 domain region, was substituted wi th Phe or Glu, Substitution of Tyr-130 with Phe enhanced the binding o f Syk to the receptor and increased receptor-mediated protein tyrosine phosphorylation, while substitution with Glu greatly reduced this int eraction, Replacement of Tyr-130 with Glu also increased the basal act ivity of the kinase, while replacement with Phe decreased its activity and uncoupled kinase activation from receptor engagement, These data suggest that the phosphorylation of Tyr-130 normally plays an importan t role in mediating both the activation of Syk and its release from th e antigen receptor.