text: Multistep-feedback loop mechanism also leads to ultrasensitivity. 
  There is paper introducing that engineering synthetic feedback loops using yeast mating mitogen-activated protein (MAP) kinase pathway as a model system.
  In Yeast mating pathway: alpha-factor activates receptor, Ste2, and Ste4 and activated Ste4 recruits Ste5 complex to membrane, allowing PAK-like kinase Ste20 (membrane-localized) to activate MAPKKK Ste11. Ste11 and downstream kinases, Ste7 (MAPKK) and Fus3 (MAPK), are colocalized on the scaffold and activation of cascade leads to transcriptional program. They used pathway modulators outside of core cascade, Ste50 promotes activation of Ste11 by Ste20; Msg5 (negative, red) is MAPK phosphatase that deactivates Fus3 (Fig.2A).
  What they built was circuit with enhanced ultrasensitive switch behavior by constitutively expressing a negative modulator, Msg5 which is one of MAPK phosphatase and inducibly expressing a positive modulator, Ste50 which is pathway modulators outside of core cascade(Fig.2B). 
  The success of this recruitment-based engineering strategy suggests that it may be possible to reprogram cellular responses with high precision.