In a living cell, Goldbeter–Koshland modules are embedded in a bigger network with upstream and downstream components. This components may constrain the range of inputs that the module will receive as well as the range of the module’s outputs that network will be able to detect. Altszyler et al. (2014)  studied how the effective ultrasensitivity of a modular system is affected by these restrictions. They found that Goldbeter–Koshland modules are highly sensitive to dynamic range limitations imposed by downstream components. However, in the case of asymmetric Goldbeter–Koshland modules, a moderate downstream constrain can produce effective sensitivities much larger than that of the original module when considered in isolation.