Figure 4

Snapshots from the integrated macrophage pathway diagram. (a) Activation of the interferon type-1 receptor through its interaction with interferon-α (IFNA) or interferon-β (IFNB1). In each case binding of the ligand causes autophosphorylation of JAK1 which eventually leads to the type1-interferon response (not shown). (b) Activation of TLR7 by single stranded RNA in the endosome. This sequential multistep process involves binding events, autophosphorylations and dissociations steps. (c) E3 ligase system. Up to 500 proteins may potentially function as E3 ligases and here the well documented members are shown. (d) Depiction of the proteasome. In some cases it is useful to lay out the subunits of a complex to reflect the complexes known structure. Represented here are the layers of the proteasome's barrel structure and cap. (e) Activation of MAPK14 (p38). Phosphorylation of p38 is reversible; numerous kinases will phosphorylate p38. p38 is dephosphorylated by DUSP1 and inhibited by the specific inhibitor SB203580. (f) Combinatorial assembly of the MHC class 2 HLA-D (alpha/beta) complexes. The & and OR Boolean operators indicate the combinatorial assembly of HLA-D (alpha/beta) complex from different classes of MHC class 2 proteins. (g) Genes activated by NFKB1 (p50):RELA (p65) complex. A number of genes activated by the binding of the p50:p65 complex to known NFKB elements in their promoter. In each case the likely functional consequence of this activation is shown as a pathway output. (h) Regulation of IFNB1 expression. Shown are the known promoter elements and factors that bind to them leading to IFNB1 expression.