Regulation and Function of Syk Tyrosine Kinase in Mast Cell Signaling and Beyond

Figure 2

ITAM-based Syk activation: activation of the immunoreceptor, here represented by a γ-subunit of FcεRI, results in the phosphorylation of the ITAMs by Lyn or other Src kinase that associates with the receptor. This recruits the cytoplasmic Syk which binds to the phosphorylated ITAM (p-ITAM) resulting in conformational changes that disrupt its autoinhibited structure, which increase the kinase activity of Syk. After activation, Syk is tyrosine phosphorylated essentially by trans- or autophosphorylation with some participation of other tyrosine kinases. The phosphorylation of Tyr-130 releases the kinase from the receptor allowing Syk to phosphorylate its targets in the cytoplasm of the cell.