Getting Syk: spleen tyrosine kinase as a therapeutic target

• Syk couples many immune recognition receptors to inflammatory responses.
• Syk is a pro-survival factor for several hematological and non-hematological cancers.
• Small-molecule inhibitors of Syk are under development for the treatment of both immune disorders and cancer.

Spleen tyrosine kinase (Syk) is a cytoplasmic protein tyrosine kinase well known for its ability to couple immune cell receptors to intracellular signaling pathways that regulate cellular responses to extracellular antigens and antigen–immunoglobulin (Ig) complexes of particular importance to the initiation of inflammatory responses. Thus, Syk is an attractive target for therapeutic kinase inhibitors designed to ameliorate the symptoms and consequences of acute and chronic inflammation. Its more recently recognized role as a promoter of cell survival in numerous cancer cell types ranging from leukemia to retinoblastoma has attracted considerable interest as a target for a new generation of anticancer drugs. This review discusses the biological processes in which Syk participates that have made this kinase such a compelling drug target.