UP-REGULATION OF ERK (MAP KINASE) AND MEM (MAP KINASE KINASE) TRANSCRIPTION AFTER RAT FACIAL-NERVE TRANSECTION

Up-regulation of ERK (extracellular signal-regulated kinase or MAP kin ase) and MEK (ERK kinase or MAPK kinase) expression after rat facial n erve injury was demonstrated by in situ hybridization histochemistry a nd immunohistochemistry. These two enzymes play roles in one of the ma jor intracellular signal cascade pathways involving receptor tyrosine kinase common to growth factor receptors, and transcription factors. S ignificant increases in ERK1 mRNA levels were observed from day 3 afte r facial nerve transection, with the highest level of expression from 1 to 2 weeks after the operation. This high level of mRNA expression t hen decreased gradually to the normal level. ERK1-like immunoreactivit y showed a similar time course to that of its mRNA expression; however , the decay profile was more prolonged. The up-regulation of MEK, the ERK kinase/MAPK kinase, was also detected by immunohistochemistry. The protein expression profiles were almost equivalent, but the MEK expre ssion was slightly advanced, suggesting that the observed up-regulatio n of MEK was not due to that of ERK. The receptor tyrosine kinase sign al transduction pathway via MEK-ERK located downstream of growth facto r receptors seems vital as a regulator of the synthesis of molecules t hat play important roles in the recovery process following injury or/a nd regeneration.