Therapeutic Targeting of the Proinflammatory IL-6-JAK/STAT Signalling Pathways Responsible for Vascular Restenosis in Type 2 Diabetes Mellitus

Figure 2

Protein domains in the IL-6 signalling pathway. sIL-6Rα comprises an Ig-like domain and two cytokine-binding modules (CBM). gp130 also has these three domains at the N-terminus, and these are followed by four fibronectin-like domains (FN-like), a transmembrane domain (TM), and intracellular box 1 and box 2 domains required for JAK binding and signalling. JAK contains a band 4.1, ezrin, radixin, moesin domain (FERM), an SH2-like domain, a pseudokinase domain (PK), and a kinase domain. STAT3 contains an N-terminal domain (NTD), coiled coil domain (CC), a DNA-binding domain (DBD), a short linker region, and then an SH2 domain. For SOCS3, this contains an NTD, kinase inhibitory region (KIR) which inhibits JAK, SH2 domain, and SOCS box responsible for recruiting components of the E3 ubiquitin ligase complex. Key phosphorylated tyrosine residues (Y) involved in signalling protein activation are indicated.