Table 1. Rate Constants for the Combined Model.

r	Description	Kinetics/Propensity	Rate Constant
1	R RL
2	RL R (only in endosome)
…	vesicle machinery		see Text S2
11	MAPK+RL MAPKp+RL
12	MAPKp MAPK (in cytoplasm)
12	MAPKp MAPK (in nucleus)
13	MAPKp MAPKp
14	MAPK MAPK

Definitions and rate constants of the signal transduction process. (*) For modelling purposes is constituted as where is an enzyme with concentration (394 molecules in the endosome) and . (**) The activation of the signalling molecule MAPK by the receptor ligand complex RL can be triggered by RL molecules either in the plasma membrane, in endocytic vesicles or in the endosome. The activation rate constant of RL in vesicles and endosomes is set to . (***) Binding rate to the surface of the nucleus (with concentration given in with respect to the volume of the cytoplasm, modelled in analogy to Equation (5a) as described in Methods). The diffusion coefficient of the signalling molecules is set to .