The binding of SYK to DAP12 induces conformational changes that result in SYK activation. Around ten autophosporylated tyrosine residues have been identified in SYK, regulating activity and serving as docking sites for other proteins. Sites include Y131 of interdomain A, Y323, Y348, and Y352 of interdomain B, Y525 and Y526 within the activation loop of the kinase domain and Y630 in the C-terminus (Zhang et al. 2002, Lupher et al. 1998, Furlong et al. 1997).
SYK is phosphorylated by Src family kinases and this acts as an initiating trigger by generating a few molecules of activated SYK, which then initiate SYK autophosphorylation (Hillal et al. 1997, Castro et al. 2010)