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

摘要

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. Affer spatial maze learning. up-regulation of c-src mRNA was observed in the CA3 region of the hippocampus, which was accompanied by increases in pp60c-src protein in hippocampal synaptosomal preparations. Training also triggered an increase in c-src protein tyrosine kinase activity that was correlated with its tyrosine dephosphorylation in the synaptic membrane fraction. After training. pp60c-src from hippocampus showed enhanced interactions with synaptic proteins such as synapsin I, synaptophysin. and the type 2 N-methyl-D-aspartate receptor, as well as the cytoskeletal protein actin. The association of pp60c-src with insulin receptor in the synaptic membrane fraction, however. was temporally decreased after training. Furthermore, in vitro results showed that Ca~2+ and protein kinase C might be involved in the regulation of protein-protein interactions of pp60c-src. These results suggest, therefore. that pp60c-src participates in the regulation of hippocampal synaptic activity during learning and memory.