Figure 2

Dynamics of cAMP, Ras2-GTP and active PKA with and without the feedback on Ira2. When the feedback control on Ira2 proteins is not activated, the dynamics of cAMP shows an initial transient increase and the successive establishment of a stable steady state (top left). In this condition, neither Ras2-GTP nor active PKA show oscillatory behavior (top right). On the contrary, when the feedback on Ira2 proteins is activated, the initial peak on cAMP amount is followed by the establishment of a stable oscillatory state (bottom left), as also reflected in the dynamics of both Ras2-GTP and of the active fraction of PKA (bottom right). In S. cerevisiae, cAMP was experimentally determined to be around 2×10⁵ molecules after stimulation, while basal levels vary from 2×10⁴ to 5×10⁴ molecules/cell; as a consequence of stimulation, a cAMP peak was observed after 45–60 s, and then a new steady-state was reached in 3–5 min (see, e.g., Figure 2 in [28]). The expected number of cAMP molecules derived from stochastic simulations was calculated here by considering our own measurements [16] and data presented in [28].