Regeneration of peripheral nerves: The role of protein phosphorylation

The involvement of phosphorylation/dephosphorylation reactions in peripheral nerve regeneration was studied in frog and adult mouse during in vivo and in vitro conditions. By comparing phosphoprotein patterns in normal and regenerating frog sciatic nerves a regeneration related phosphoprotein (PP90) was found. The kinase acting on PP90 was pharmacologically distinguished from PKC and PKA but sensitive to the purine analogues 6- thioguanine and 2-aminopurine. The same compounds inhibited regeneration of the frog nerve which raised the possibility that a purine analogue sensitive kinase is involved in the regeneration process. The importance of phosphatases was studied by the use of the phosphatase inhibitor okadaic acid. The compound potently blocked the regeneration exerting its effects locally in the outgrowth region, presumably via interaction with the growth cones. Experiments using adult mouse peripheral nerves addressed the role of the mitogen activated protein (MAP) kinase pathway in the axonal outgrowth process. Both the MAP kinase protein and activity were found to increase following nerve injury and subsequent regeneration. Furthermore, the outgrowth was reduced when the MAP kinase pathway was inhibited by [2-(21amino-31-methoxyphenyl)-oxanaphthalen-4-one] (PD), which interacts with the activation of this enzyme. The results show the involvement of the MAP kinase pathway in peripheral nerve regeneration.