Specific Features of Transient Ras and Sustained Rap1 Activation

Epidermal growth factor (EGF) and nerve growth factor (NGF) induce transient and sustained extracellular signal-regulated kinase (ERK) activation, respectively, and regulate cell growth and differentiation in PC12 cells (Fig. 1a) (Gotoh et al. 1990; Qiu and Green 1992; Traverse et al. 1992; Vaudry et al. 2002). Transient and sustained ERK activation in PC12 cells depends on transient Ras activation and sustained Rap1 activation, respectively (Fig. 1b) (Vaudry et al. 2002; York et al. 1998). We have previously modeled EGF- and NGF-dependent ERK activation in PC12 cells, and found that transient Ras and consequent ERK activation depends on rapidly increasing rates of EGF and NGF, whereas sustained Rap1 and consequent ERK activation depends on the final concentration of NGF (Sasagawa et al. 2005). We here construct simple Ras and Rap1 models whose inactivation is dependent on and independent of stimulation, respectively (Fig. 1c), and summarize how the modes of inactivation of Ras and Rap1 makes the features distinct.