Figure 3.

The molecular mechanism by which suppressor of cytokine signaling 1 (SOCS1) and SOCS3 negatively regulate Janus kinase (JAK) activation. SOCS1 binds to the JAKs and inhibits catalytic activity; SOCS3 binds to JAK-proximal sites on cytokine receptors and inhibits JAK activity through KIR (kinase inhibitory region). These complexes may be degraded by ubiquitination and proteasomal degradation recruited through the SOCS box.