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.
Yoshimura et al. Arthritis Research & Therapy 2005 7:100-110 doi:10.1186/ar1741