The nucleus shuns MAPK

Upon differentiation, many cell types no longer proliferate in response to growth factor–activated MAPK. But MAPK has more than just mitogenic effects, and the cells must still activate and respond to MAPK to adjust lipid metabolism, protein synthesis, and other cellular functions. On page 689, Smith et al. identify a simple, yet until now elusive, mechanism by which cells uncouple MAPK's proliferative effects from its other functions.

The strategy is based on compartmentalization. To bring about cell division, MAPK phosphorylates nuclear substrates such as Elk-1. But its nonproliferation substrates are cytoplasmic. So the simple fix to stop division in differentiated cells, as Smith and colleagues show, is to prevent MAPK from entering the nucleus. The group uses retinoic acid to induce differentiation in both embryonic stem cells and an embryonic carcinoma cell...