Percentage of parameter space where bistable responses are possiblea.

aSome bidimensional sections of the multidimensional parameter space of bistability are shown in Figure S2. The results show that in TCS with a bifunctional SK, both a TCSK and a TCRR cause a decrease in the size of the parametric region of bistability, with one exception: Model C has a larger parametric region of bistability when the signaling target is SK autophosphorylation (k1). However, in systems with a monofunctional SK, a TCSK causes an increase and a TCRR causes a decrease in the size of the parametric region of bistability if the environment modulates the SK dephosphorylation (k2). A|B stands for Model A controlled for Model B. A|C stands for Model A controlled for Model C.