Syk

The Syk family of non-receptor tyrosine kinases comprises SYK and ZAP70, the key signal transducers of immune receptors. Both contain tandem N-terminal SH2 domains that bind the doubly phosphorylated ITAM motifs within immunoreceptor chains, unleashing their kinase domains and recruiting adapters such as LAT and SLP-76. ZAP70 is essentially restricted to T lymphocytes, where it transduces T-cell receptor signals for thymocyte development and antigen responses. SYK is broadly expressed, mediating B-cell receptor signaling, myeloid Fc receptor and C-type lectin responses, and platelet activation via the collagen receptor GPVI. Consequently, SYK inhibition with fostamatinib treats chronic immune thrombocytopenia, while ZAP70 expression serves as a prognostic marker in chronic lymphocytic leukemia.