<p>(A) The sketch is related to the GPCR signaling pathway. The pathway in blue are the skeleton of the forward module depicting how signals propagate forward. Feedback modules in red indicate multiple regulations. The RGS in Module 3 drive two proteins: G<i>α</i>i-GTP and G<i>α</i>q-GTP into the off state: G<i>α</i>i-GDP and G<i>α</i>q-GDP. Reactions in Module 2 constitute a reaction chain, that is: IP3—> IP4—> IP5—> PIP2, and hence reduce the concentration of IP3. Module 2 and 3 are local feedbacks while Module 4 and 5 are working together serving as a global feedback module (B) The skeleton of the EGFR induced MAPK signaling network. Module 4, 5, 6 are three joint dephosphorylation feedback cycles. Module 4 is engaged in the dephosphorylation of ERK-PP, while Module 5 and 6 are able to convert MEK-PP and Raf* to MEK and Raf. Module 8 is also a local feedback serving as a buffer for the highly regulated compounds: (EGF-EGFR*)<sub>2</sub>-GAP-Grb2-Sos, (EGF-EGFR*)<sub>2</sub>-GAP-Shc*-Grb2-Sos. It also takes in the upstream protein Ras-GTP* and feeds the Ras-GDP back. Two global feedback modules reside near the end of the network. (C) A simplified plot of the JAK/STAT signaling network. The binding of the IFN-<i>γ</i> to its receptor causes activation of the transcription factor (STAT1n*)<sub>2</sub>. The expression product SOCS1 suppresses signaling. SHP-2, serving as a tyrosine phosphatase in Module 3, can directly sequester the activation of (IFN-R-JAK*)<sub>2</sub>. PPN (nuclear phosphatase TC45) involved in Module 2, and PPX (cytoplasmic phosphatase) embedded in Module 1 act in the same way to capture (STAT1n*)<sub>2</sub> or (STAT1c*)<sub>2</sub> and feed the inactive STAT1 back to the forward module.</p
