SYK (Spleen tyrosine kinase), along with Zap-70, is a member of the Syk family of cytoplasmic tyrosine kinases that contain a dual SH2 domain separated by a linker region. In B cells, SYK couples the B-cell antigen receptor (BCR) to the mobilization of calcium ion either through a phosphoinositide 3-kinase-dependent pathway, when not phosphorylated on tyrosines of the linker region, or through phosphorylation/activation of phospholipase C-gamma, when phosphorylated on Tyr-348 and Tyr-352. Phosphorylation on Tyr-323 creates a binding site for c-Cbl, which is a negative regulator of BCR-stimulated calcium signaling. Also transmits signals from other cell surface receptors including the T-cell receptor, CD74, Fc receptor, and integrins. Abnormal constitutive SYK activity has been implicated in some hematopoietic malignancies.