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

Figure 4

The IL-6–JAK/STAT–SOCS3 signalling pathway. The principal signalling pathway triggered by IL-6 is the JAK/STAT pathway (orange). JAK phosphorylates gp130 leading to phosphorylation and dimerisation of STAT, which translocates to the nucleus to induce expression of prosurvival and proinflammatory genes. It also induces expression of SOCS3 as a negative feedback loop to switch off the signalling pathway (green). SOCS3 forms part of the E3 ubiquitin ligase complex to ubiquitinate JAK, leading to proteasomal degradation and termination of the signalling cascade. JAK can also act independently of STAT to trigger additional mitogenic and growth-promoting effects via the PI3K/Akt and ERK1/2 pathways (blue). Sites of action of specific therapeutic inhibitors are indicated in red boxes.