Figure 3. NF-κB as an example molecular network.
A simplified network for the canonical NF-κB pathway consisting of active IKK, IκBα, and NF-κB are represented in a navigational map (A) and in a schematic diagram (B). Many upsteam signals (factors like Tumor Necrosis Factor-α, Interleukin-1, and Lipopolysaccharide, or cell surface receptor signaling from T cell/B cell receptors) induce the kinase activity of IKK. Phosphorylation of two specific serines in IκBα by IKK initiates the degradation of IκBα by the proteasome. Free NF-κB then translocates to the nucleus and activates IκBα gene transcription. Newly synthesized IκBα binds to NF-κB in the nucleus or in the cytoplasm. Numerous molecular mechanisms down-regulate the post-stimulus kinase activity of IKK. IKKO indicates an inactive form without catalytic activity. NF-κBnuc represents the nuclear species. NF-κB itself exists most predominantly as a heterodimer of p65 (transcriptionally active) and p50 subunits. Symbols were used in the navigational map (A) according to the WIRE guideline: Briefly, a circle indicates a protein molecule. Boxed circles are protein complexes. A ‘+’ sign in an arrow represents a positive (activating) effect.