SOCS

SOCS is the acronym ofSuppressors of Cytokine Signalling. In interferon-induced signal processing, in addition to activating factors, important negative feedback mechanisms interact to attenuate STAT phosphorylation and ISG expression several hours after IFN stimulation. These factors include members of the Suppressors of Cytokine Signalling Protein family(SOCS), in particular SOCS1. SOCS1 acts like a negative feedback loop for IFN-I signalling , by directly inhibiting JAK tyrosine kinase activity via its kinase inhibitory region.

The development and activity of our immune system is largely controlled by the action of pleiotropic cytokines and growth factors, small secreted proteins that bind to receptors on the surface of immune cells to elicit an appropriate physiological response. Cytokine signaling is predominantly carried out by intracellular proteins known as Janus kinases (JAKs) and the Signal Transducers and Activators of Transcriptions(STATs). Although the "inner workings" of cytokine-activated signaling pathways are well known, the nuanced ways in which different cellular outcomes are achieved and the precise molecular details of the proteins that regulate or inhibit these pathways are still being explored (Linossi EM et al. 2018) .

This is exemplified by the intricate role of suppressor of cytokine signaling (SOCS) proteins. SOCS proteins act as negative feedback inhibitors by dampening specific cytokine signals to prevent excessive cellular responses and return the cell to a homeostatic state. Numerous studies have shown that they can inhibit these signaling pathways at the receptor complex, either by directly inhibiting JAK activity or by targeting the receptor complex for proteasomal degradation.

For many of the SOCS, information is still lacking , allowing confident identification of the full set of tyrosine phosphorylated targets of their SH2 domain (Linossi EM et al. 2018).

1. Kile BT et al (2001) The suppressors of cytokine signalling (SOCS). Cell Mol Life Sci 58:1627-1635.
2. Linossi EM et al (2018) Understanding SOCS protein specificity. Growth Factors 36:104-117.