DIFFERENTIATION OF PC12 CELLS IN RESPONSE TO A CAMP ANALOG IS ACCOMPANIED BY SUSTAINED ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE - COMPARISON WITH THE EFFECTS OF INSULIN, GROWTH-FACTORS AND PHORBOL ESTERS

It has been proposed previously that the sustained activation of mitog en-activated protein kinase may be necessary for the differentiation o f PC12 cells. Differentiation of PC12 cells is induced by many extrace llular agonists including nerve growth factor (NGF) and cyclicAMP anal ogues, but not epidermal growth factor (EGF), insulin or phorbol ester s. Our results demonstrate that: (i) 8-(4-chlorophenylthio)-cyclicAMP (CPT-cAMP) activates MAP kinase; this raises the possibility that the MAP kinase pathway may be activated by agents that act through adenyla te cyclase; (ii) NGF and CPT-cAMP as well as phorbol esters promote su stained activation of MAP kinase. This suggests that while sustained M AP kinase activation may be associated with differentiation it may not be sufficient, and that other as yet unidentified parallel pathways m ay be involved.