Fyn is a member of the Src family of non-receptor tyrosine kinases259 and is expressed throughout the brain, with moderate expression in the amygdala, NAc, VTA, and midbrain.6 Fyn is composed of six domains: an Src homology region that contains lipid modification sites, a unique region, SH2 and SH3 domains, a catalytic domain, and a short auto-inhibitory tail. Fyn is constitutively inactive, a state that is maintained by blockade of the catalytic region by the SH2 and SH3 domains and the auto-inhibitory tail. Phosphorylation at Tyr-527 maintains the interaction of the SH2 region with the catalytic domain. Activation of Fyn involves dephosphorylation of Tyr-527 and release of the SH2 and SH3 domains and auto-inhibitory tail from the catalytic domain, as well as autophosphorylation at Tyr-416.259 Fyn activation is commonly measured as an increase in autophosphorylation at Tyr-416.
