ACTIVATION OF MAP KINASE KINASE IS NECESSARY AND SUFFICIENT FOR PC12 DIFFERENTIATION AND FOR TRANSFORMATION OF NIH 3T3 CELLS

The MAP kinase pathway is activated by a wide variety of external sign als leading to cell proliferation or differentiation. However, it is n ot clear whether activation of this pathway is required for cellular r esponses or whether it is only one branch point in signal transduction . To investigate these questions, we generated constitutively activate d and interfering mutants of MAP kinase kinase 1. The activated mutant s stimulated PC12 cell neuronal differentiation and transformed NIH 3T 3 cells. The interfering mutants inhibited growth factor-induced PC12 differentiation, growth factor stimulation of proliferation, and rever ted v-src- and ras-transformed cells. These results therefore show tha t, depending on cellular context, activation of MAP kinase kinase is n ecessary and sufficient for cell differentiation or proliferation.