Syk is a protein tyrosine kinase that plays an important role in intracellular signal transduction in hematopoietic cells. Syk interacts with immunoreceptor tyrosine-based activation motifs located in the cytoplasmic domains of immune receptors. It couples the activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. There is also evidence of a role for Syk in nonimmune cells and investigators have indicated that Syk is a potential tumor suppressor in human breast carcinomas. Tyr323 is a negative regulatory phosphorylation site within the SH2-kinase linker region in Syk. Phosphorylation at Tyr323 provides a direct binding site for the TKB domain of Cbl. Tyr352 of Syk is involved in the association of PLCγ1. Tyr525 and Tyr526 are located in the activation loop of the Syk kinase domain; phosphorylation at Tyr525/526 of human Syk is essential for Syk function.
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