Figure 1

CADBIOM model for the canonical TGF-β pathway. (A) Schematic representation of the canonical pathway. Binding of TGF-β to the receptor induces recruitment and phosphorylation of Smad2/3. Activated Smad2/3 heterodimerizes with Smad4 and the complex migrates to nucleus where it regulates gene transcription. (B) Two examples of translations from the PID database (left) into the CADBIOM representation (right). Top: interaction of Smad2/3 with Smad4. The CADBIOM representation uses two transitions from a component toward the complex, conditioned by the presence of the other component and leading to the synchronization of the transition. The same event h1 is associated with the two transitions that occur simultaneously. Bottom: migration of the Smad complex to the nucleus. The CADBIOM representation uses a transition between the two places “SMAD3_SMAD4_active_cytoplasm” and “SMAD3_SMAD4_active_nucleus” conditioned by the presence of importins within the guard. The event h1 indicates the timing of the transition. (C) CADBIOM illustration of the canonical pathway after integration of the three PID pathways: “TGF-β receptor signaling” (PID Ref: tgfbrpathway), “regulation of cytoplasmic and nuclear Smad2/3 signaling” (PID Ref: Smad2-3pathway) and “regulation of nuclear Smad2/3 signaling” (PID Ref: Smad2-3nuclearpathway).