Table 1.

The functions of SOCS3

Role	Mechanism
Inhibits JAK/STAT signalling	Binds to JAKs via SH2 domain and inhibits activity Competes for phosphorylation sites on cytokine receptors and inhibits STAT activation Ubiquitinates and degrades JAKs via SOCS box
Inhibits Ras/extracellular signal-regulated kinase (Ras/ERK) signalling	Interacts with the Ras inhibitor; p120 RasGAP Maintains activation of ERK Ensures cell survival and proliferation
Inhibits phosphatidylinositide 3-kinases (PI3K) signalling	Prevents PI3K p85 activation
Inhibits focal adhesion kinase (FAK) signalling	Interacts with FAK (Y397) via SH2 and KIR domains Inhibits kinase activity and phosphorylation of FAK Ubiquitinates and degrades FAK via SOCS box Inhibits cell motility on fibronectin
Inhibits NF-κB pathway	IL-1β-induced NF-κB-dependent pro-apoptotic early response genes are inhibited by SOCS-3, e.g. iNOS, ICAM, complement C3, Mob-1, MIP-1, CX3C, NF-κB-p105, IRF-1 and fibrinogen
T helper (Th) cell polarisation	Highly expressed in Th2 cells Prevents differentiation into Th1 cells Restricts IL-17 induction