Spleen tyrosine kinase (SYK) is the key mediator of CLEC7A's (Dectin-1) downstream cellular responses, such as cytokine production and induction of the respiratory burst (Brown 2006). A phosphorylated tyrosine in CLEC7A provides the docking site for SYK. In contrast to usual ITAM receptors where dually phosphorylated tyrosines are necessary for SYK recruitment, phosphorylation of only the membrane proximal tyrosine is sufficient for SYK association with CLEC7A. Binding of SYK to the phosphorylated ITAM motif is sufficient to fully activate SYK (Tsang et al. 2008). SYK deficiency or SYK inhibitors inhibit CLEC7A-dependent cytokine production, MAPK activation and NF-kB activation, suggesting that SYK is essential for CLEC7A signalling (Rogers et al. 2005, Underhill et al. 2005, Fuller et al. 2007). Activation of NF-kB by SYK can be categorised into both canonical (c-Rel and p65) and NIK (NF-kB inhibitory kinase)-dependent non-canonical (RelB) routes (Gringhuis et al. 2009).