SOCS Structure

SOCS structure consists of a central Src homology 2 domain (SH2), an amino end terminal which is variable and a conserved carboxyl terminal domain known as the SOCS box1,26,60. SOCS 1 and 3 also have a kinase inhibitory domain (KIR) located adjacent to the SH2 domain which is used to inhibit JAKs62,66.
SOCS regulate JAK/STAT pathway in three ways. The first method is that SOCS associate with phosphorylated tyrosine residues on JAKs to prevent JAKs phosphorylating the cytokine receptor which allows STATs to bind so JAKs can phosphorylate and activated them. SOCS bind to the JAKs via their KIR domain1,58. The Secondly SOCS associate with the phosphorylated tyrosine residues on the cytokine receptors to prevent STATs from binding and becoming phosphorylated by JAKs1,22. The SH2 domain is responsible for the binding of tyrosine

SOCS1 uses its E3 ubiquitin ligase to tag the proteins for proteolysis1 but also binds to JAKs to inhibit catalytic activity8,5. SOCS1 is therefore an inhibitor for the pro-inflammatory pathway which leads to M1 activation. SOCS1 can be induced by IL6 signalling through STAT3 and IL4/IL13 signalling through STAT6 to inhibit the IFN- γ, JAK 2, STAT1 pathway52,63,55,56. A high SOCS1 to SOCS3 ratio is also an indicator for M2 macrophages as SOCS1 also controls the signalling of IL4 and IL13 through STAT6 which controls M2 activation. SOCS1 is therefore anti-inflammatory due to its role in regulating and attenuating M1 activation and controlling M2 activation1. As SOCS1 is involved in both M1 and M2 control, it is known as a molecular switch57. When SOCS1 is deficient there is an increase of SOCS3 in macrophages1 and uncontrolled pro-inflammatory response due to excessive IL6 and TNF-α production65 which leads to autoimmune