Interactions between Src family protein tyrosine kinases and PSD-95.

Five members of the Src family of non-receptor protein tyrosine kinases--Lck, Lyn, Fyn, Src, and Yes--are known to be expressed in the central nervous system. Src and Fyn have been shown to play important roles in synaptic transmission and plasticity at excitatory synapses. Here we investigate the subcellular distribution and potential binding partners of Src family protein tyrosine kinases in brain, focusing on the lesser studied kinases Lck, Lyn, and Yes. We find that Lck, Lyn, and Yes are localized to the postsynaptic density (PSD), the primary structural component of excitatory synapses. Lyn and Yes, as well as Src, but not Lck physically associate with the prominent PSD scaffolding protein PSD-95 in co-immunoprecipitation experiments. Further, we demonstrate that PSD-95 GST fusion proteins bind directly to purified recombinant Lyn, Src, and Yes in vitro. In addition, we show that PSD-95 is unique among PSD-95 family members in that the other members, PSD-93, SAP97, and SAP102, do not physically associate with Lyn, Src, or Yes. Together our results suggest that PSD-95 may be important for localizing and/or regulating multiple Src protein tyrosine kinases at the NMDA receptor multiprotein complex.