By contrast, the sustained response was dominated by the levels of Rap1 activation. Rap1-GAP activity was constitutive rather than inducible, so the overall response depended only on how much activator was supplied by the growth factor receptor. High constant levels of NGF (and a lack of the degradation seen with the EGF receptor) gave sustained ERK activation necessary for PC12 differentiation.
Thus, Ras and Rap1 capture transient and sustained receptor activation, respectively. This is translated into either transient or sustained ERK activation. Kuroda and colleagues are now looking at how this difference in the persistence of ERK activity is converted into distinct cellular behaviors.