The non-receptor-type Src tyrosine kinases are key components of intracellular signal transduction that are expressed at high levels in the nervous system. To improve understanding of the cascades of molecular events underlying peripheral nerve regeneration, we analyzed active Src expression in the crushed or cut rat sciatic nerves using a monoclonal antibody (clone 28) that recognizes the active form of Src tyrosine kinases, including c-Src and c-Fyn. Western blots showed that active Src expressed in the normal sciatic nerve transiently increased up to threefolds after both types of injury. Immunohistochemistry using clone 28 showed that axonal components are the primary sites of active Src expression in the normal sciatic nerve. Soon after both types of injury, active Src was abundantly expressed in Schwann cells of the segments distal to the injury site. The expression of active Src in the cells decreased with restoration of the axon-Schwann cell relationship and eventually became depleted to very low levels after crushing, but was sustained at high levels in the cut model until the end of the experiment. Regenerated axons consistently expressed active Src throughout nerve regeneration and these eventually became the major sites of active Src expression in the crushed nerve. Among the Src tyrosine kinases, active c-Src selectively increased after crushing according to immunoprecipitation and immunoblotting analyses. Due to its potent biological activity, the increased amounts of the active form of Src probably enhance axonal regrowth, the Schwann cell response, and axon-Schwann cell contact for peripheral nerve regeneration.
Animals Axons