Nonreceptor tyrosine protein kinase pp60c-src in spatial learning: Synapse-specific changes in its gene expression, tyrosine phosphorylation, and protein-protein interactions

c-src is a nonreceptor tyrosine protein kinase that is highly concentrated in synaptic regions, including synaptic vesicles and growth cones. Here, we report that the mRNA signal of pp60c-src is widely distributed in the rat brain with particularly high concentrations in the hippocampus. After spati al maze learning, up-regulation of c-src mRNA was observed in the CA3 regio n of the hippocampus, which was accompanied by increases in pp60c-src prote in in hippocampal synaptosomal preparations. Training also triggered an inc rease in c-src protein tyrosine kinase activity that was correlated with it s tyrosine dephosphorylation in the synaptic membrane fraction, After train ing, pp60c-src from hippocampus showed enhanced interactions with synaptic proteins such as synapsin I, synaptophysin, and the type 2 N-methyl-D-aspar tate receptor, as well as the cytoskeletal protein actin, The association o f pp60c-src with insulin receptor in the synaptic membrane fraction, howeve r, was temporally decreased after training. Furthermore, in vitro results s howed that Ca2+ and protein kinase C might be involved in the regulation of protein-protein interactions of pp60c-src. These results suggest, therefor e, that pp60c-src participates in the regulation of hippocampal synaptic ac tivity during learning and memory.